Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   
X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

ATM (ataxia telangiectasia mutated)

Written1998-04Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France
Updated1999-10Nancy Uhrhammer, Jacques-Olivier Bay, Richard A Gatti
Centre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France
Updated2002-11Nancy Uhrhammer, Jacques-Olivier Bay, Richard A Gatti
Centre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France
Updated2016-10Yossi Shiloh
The David and Inez Myers Chair in Cancer Research, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; yossih@post.tau.ac.il

Abstract Review on ATM, with data on DNA, on the protein encoded, and where the gene is implicated.

Keywords Ataxia telangiectasia ; Cerebellar ataxia; Telangiectasia; Immunodeficiency; T- cell malignancies; B-cell malignancies; Carcinomas; Senescence; Chromosome instability syndrome; DNA double-strand breaks; Translocation; Oxidative stress; Homeostasis; ATM; chromosome.

(Note : for Links provided by Atlas : click)

Identity

Alias_namestelomere maintenance 1
homolog (S. cerevisiae)
Alias_symbol (synonym)TEL1
TELO1
Other alias
HGNC (Hugo) ATM
LocusID (NCBI) 472
Atlas_Id 123
Location 11q22.3  [Link to chromosome band 11q22]
Location_base_pair Starts at 108222832 and ends at 108369099 bp from pter ( according to hg19-Feb_2009)  [Mapping ATM.png]
Fusion genes
(updated 2016)		ATM (11q22.3) / ASPH (8q12.3)ATM (11q22.3) / ATM (11q22.3)ATP6V1C2 (2p25.1) / ATM (11q22.3)
CUX1 (7q22.1) / ATM (11q22.3)JARID2 (6p22.3) / ATM (11q22.3)
Note See also, in Deep Insight section: Ataxia-Telangiectasia and variants.

DNA/RNA

 
  ATM (11q22.3) in normal cells: PAC 1053F10 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Description The ATM gene extends over 184 kb and contains 66 exons producing a 13 kb mRNA (Uziel T et al., 1996; Platzer M et al., 1997); numerous Alu and Lime sequences.
Transcription Alternative exons 1a and 1b; initiation codon lies within exon 4; 12 kb transcript with a 9.2 kb of coding sequence.
The ATM promotor is bi-directional and also directs the transcription of the NPAT gene.

Protein

Description ATM is a homeostatic protein kinase with an extremely broad range of roles in various cellular circuits (Shiloh Y et al., 2013; Guleria A et al., 2016; Shiloh Y, 2014; Cremona CA et al., 2014; Ambrose M et al., 2013; Espach Y et al., 2015; Awasthi P et al., 2016). This large polypeptide of 350 kDa and 3,056 residues bears a PI3 kinase signature within its carboxy-terminal catalytic site, but has the catalytic activity of a serine-threonine protein kinase. This motif is characteristic of a protein family of which ATM is a member - the PI-3 kinase-like protein kinases (PIKKs; Lovejoy CA et al., 2009; Baretić D et al., 2014).
This family also contains the MTOR protein, which regulates many signaling pathways in response to nutrient levels, growth factors and energy balance (Alayev A et al., 2013; Cornu M et al., 2013); the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), which is involved in the NHEJ pathway of double strand breaks (DSB) repair and other genotoxic stress responses (Davis AJ et al., 2014; Jette N et al., 2015), SMG1, which plays a key role in nonsense-mediated mRNA decay (Yamashita A, 2013); and ATR, which responds to stalled replication forks and a variety of DNA lesions that lead to the formation of single-stranded DNA, including deeply resected DSBs (Errico A et al., 2012; Maréchal A et al., 2013; Awasthi P et al., 2016). The redundancy, crosstalk and collaboration between the latter three PIKKs, which collectively respond to a broad spectrum of genotoxic stresses, are being extensively investigated (Lovejoy CA et al., 2009; Maréchal A et al., 2013; Sirbu BM et al., 2013; Thompson LH, 2012; Gobbini E et al., 2013; Chen BP et al., 2012).
It should be noted that in A-T patients, the two PIKKs that converse and cooperate with ATM in the response to genotoxic stress, ATR and DNA-PK, remain active. In view of the functional relationships between the three protein kinases, some of ATM's duties are probably carried out to a certain extent by ATR and/or DNA-PK, in A-T cells. On the other hand, the lack of a very versatile member of this trio may lead to some suboptimal responses of the other two, if they depend on the crosstalk with ATM. This interesting question is a subject of intensive research.
Expression ATM is expressed in all tissues.
Localisation Mostly in the nucleus throughout all stages of the cell cycle.
Function Homeostatic protein kinase involved in many cellular circuits. A primary role in the DNA damage response. Activated vigorously by DNA double-strand breaks and activates a broad network of responses. ATM initiates cell cycle checkpoints in response to double-strand DNA breaks by phosphorylating TP53, BRCA1, H2AFX ID: 40783, ABL1,NFKBIA and , as well as other targets; in certain types of tissues ATM inhibits radiation-induced, TP53-dependent apoptosis.
  • Double strand breaks. The most widely documented function of ATM, and the one associated with its most vigorous activation, is the mobilization of the complex signaling network that responds to DSBs in the DNA (Shiloh Y et al., 2013; Cremona CA et al., 2014; Awasthi P et al., 2016; Thompson LH, 2012; McKinnon PJ, 2012). DSBs are induced by exogenous DNA breaking agents or endogenous reactive oxygen species (Schieber M et al., 2014), and are an integral part of physiological processes including meiotic recombination (Borde V et al., 2013; Lange J et al., 2011) and the rearrangement of antigen receptor genes in the adaptive immune system (Alt FW et al., 2013). DSBs are repaired via nonhomologous end-joining (NHEJ), or homologous recombination repair (HRR; Shibata A et al., 2014; Chapman JR et al., 2012; Jasin M et al., 2013; Radhakrishnan SK et al., 2014). DSBs also activates the DDR, a vast signaling network that mobilizes special cell cycle checkpoints, extensively alters the cellular transcriptome, and changes the turnover, activity and function of numerous proteins that ultimately leads to modulation of numerous cellular circuits. This network is based on a core of dedicated DDR players and the ad-hoc recruitment of proteins from many other arenas of cellular metabolism, which typically undergo special, damage-induced post-translational modifications (PTMs; Shiloh Y et al., 2013; Sirbu BM et al., 2013; Thompson LH, 2012) (Goodarzi AA et al., 2013; Panier S et al., 2013; Polo SE et al., 2011).
    Once ATM mobilizes the vast DDR network in response to a DSB (McKinnon PJ, 2012; Shiloh Y et al., 2013; Bhatti S et al., 2011), its protein kinase activity is rapidly enhanced, and PTMs on the ATM molecule are induced, including several autophosphorylations and an acetylation (Shiloh Y et al., 2013; Bhatti S et al., 2011; Bakkenist CJ et al., 2003; Kozlov SV et al., 2006; Bensimon A et al., 2010; Sun Y et al., 2007; Kaidi A et al., 2013; Paull TT, 2015).
    ATM subsequently phosphorylates key players in various arms of the DSB response network (Shiloh Y et al., 2013; Bensimon A et al., 2010; Matsuoka S et al., 2007; Mu JJ et al., 2007; Bensimon A et al., 2011), including other protein kinases that in turn phosphorylate still other targets (Bensimon A et al., 2011).
  • Single-strand break repair and base excision repair. A broader, overarching role for ATM in maintaining genome stability was recently suggested in addition to mobilizing the DSB response (Shiloh Y, 2014). According to this conjecture, ATM supports other DNA repair pathways that respond to various genotoxic stresses, among them single-strand break repair (SSBR; Khoronenkova SV et al., 2015) and base excision repair (BER) - a cardinal pathway in dealing with the daily nuclear and mitochondrial DNA damage caused by endogenous agents (Wallace SS, 2014; Bauer NC et al., 2015).
    ATM's involvement in these processes is based on its ability to phosphorylate proteins that function in these pathways. In this way ATM also takes part also in resolving non-canonical DNA structures that arise in DNA metabolism, and in regulating other aspects of genome integrity such as nucleotide metabolism, the response to replication stress, and resolution of the occasional conflicts that arise between DNA damage and the transcription machinery. ATM is not critical for any of these processes in the same way it is for the DSB response, but rather contributes to their regulation (in most cases, their enhancement) when the need arises (Shiloh Y, 2014; Segal-Raz H et al., 2011; Zolner AE et al., 2011).
    This function of ATM may explain the moderate, variable sensitivity of ATM-deficient cells to a broad range of DNA damaging agents. Among them are UV radiation, alkylating agents, crosslinking agents, hydrogen peroxide, 4-Nitroquinoline 1-oxide, phorbol-12-myristate-13-acetate and topoisomerase 1 poisons (Yi M et al., 1990; Ward AJ et al., 1994; Hoar DI et al., 1976; Paterson MC et al., 1976; Smith PJ et al., 1980; Mirzayans R et al., 1989; Henderson EE et al., 1980; Scudiero DA, 1980; Jaspers NG et al., 1982; Teo IA et al., 1982; Barfknecht TR et al., 1982; Fedier A et al., 2003; Leonard JC et al., 2004; Lee JH et al., 2006; Zhang N et al., 1996; Smith PJ et al., 1989; Alagoz M et al., 2013; Katyal S et al., 2014; Speit G et al., 2000; Shiloh Y et al., 1985; Hannan MA et al., 2002).
    ATM-deficient cells also exhibit reduced efficiency in resolving TOP1 (Topoisomerase I) -DNA covalent intermediates (Alagoz M et al., 2013; Katyal S et al., 2014).
    This ongoing role of ATM is its routine function in the daily maintenance of genome stability, while its powerful role in the DSB response is reserved for when this harmful lesion interferes with the daily life of a cell. Thus, when ATM is missing, not only is there markedly reduced response to DSBs, the ongoing modulation of numerous pathways in response to occasional stresses becomes suboptimal. All of these lesions are part of the daily wear and tear on the genome that contributes to ageing.
    An additional role for ATM in genome dynamics was proposed following evidence that ATM is involved in shaping the epigenome in neurons by regulating the localization of the histone deacetylase 4 (HDAC4; Li J et al., 2012; Herrup K et al., 2013; Herrup K, 2013), targeting the EZH2 component of the polycomb repressive complex 2 (Li J et al., 2013), and regulating the levels of 5-hydroxymethylcytosine in Purkinje cells (Jiang D et al., 2015).
  • Oxidative stress/Cellular homeostasis.
    Cytoplasmic fraction of ATM. ATM's role in cellular homeostasis is further expanded by its cytoplasmic fraction. Specifically, cytoplasmic ATM was found to be associated with peroxisomes (Watters D et al., 1999; Tripathi DN et al., 2016; Zhang J et al., 2015) and mitochondria (Valentin-Vega YA et al., 2012). In view of the evidence of increased oxidative stress in ATM-deficient cells, it has long been suspected that ATM senses and responds to oxidative stress (Gatei M et al., 2001; Rotman G et al., 1997; Rotman G et al., 1997; Barzilai A et al., 2002; Watters DJ, 2003; Takao N et al., 2000; Alexander A et al., 2010). This conjecture was validated by work from the Paull lab (Guo Z et al., 2010a), which identified an MRN-independent mode of ATM activation, differentiating it from DSB-induced activation, stimulated by reactive oxygen species (ROS) and leading to ATM oxidation (Paull TT, 2015; Guo Z et al., 2010a; Guo Z et al., 2010b; Lee JH et al., 2014). ATM was also found to be involved specifically in the protection against oxidative stress induced by oxidized low-density lipoprotein (Semlitsch M et al., 2011). It has thus assumed the role of a redox sensor (Ditch S et al., 2012; Tripathi DN et al., 2016; Krüger A et al., 2011). Recently, the first phospho-proteomic screen was carried out to identify substrates of ROS-activated ATM (Kozlov SV et al., 2016). An important arm of the ATM-mediated response to ROS extends to peroxisomes (Tripathi DN et al., 2016). Work from the Walker lab showed that ROS-mediated activation of peroxisomal ATM leads to ATM-mediated phosphorylation of LKB and subsequent activation of AMPK and TSC2, which dampens mTORC1-mediated signaling, eventually decreasing protein synthesis and enhancing autophagy (Alexander A et al., 2010; Tripathi DN et al., 2013; Zhang J et al., 2013; Alexander A et al., 2010; Alexander A et al., 2010). Further work from this lab (Zhang J et al., 2015) showed that ATM also phosphorylates the peroxisomal protein PEX5, flagging it for ubiquitylation and subsequent binding to the autophagy adapter, SQSTM1 (p62), in the process of autophagy-associated peroxisome degradation (pexophagy) - a critical process in peroxisome homeostasis (Till A et al., 2012).
    Mitochondrial fraction of ATM. Still another arm of the ATM-mediated response to oxidative stress operates in the mitochondrial fraction of ATM. ATM is thus emerging also as a regulator of mitochondrial homeostasis. Evidence is accumulating of its involvement in mitochondrial function, mitophagy, and the integrity of mitochondrial DNA (Valentin-Vega YA et al., 2012; Ambrose M et al., 2007; Eaton JS et al., 2007; Fu X et al., 2008; Valentin-Vega YA et al., 2012; D'Souza AD et al., 2013; Sharma NK et al., 2014) and further work is needed to identify its substrates in mitochondria and the mechanistic aspects of its action in this arena.
  • Links between ATM and the SASP (senescence-associated secretory phenotype). Several laboratories recently described direct links between ATM and the SASP - a cardinal feature of cell senescence. Work from the Gamble lab (Chen H et al., 2015) showed that the histone variant macroH2A.1 is required for full transcriptional activation of SASP-promoting genes, driving a positive feedback loop that enhances cell senescence. This response is countered by a negative feedback loop that involves ATM activation by endoplasmic reticulum stress, elevated ROS levels or DNA damage. ATM's activity is required for the removal of macroH2A.1 from sites of SASP genes, thus leading to SASP gene repression. The Elledge lab identified a major SASP activator - the transcription factor GATA4, whose stabilization drives this process (Kang C et al., 2015). Importantly, the activation of this pathway was dependent on both ATM and ATR, as was senescence-associated activation of TP53 and CDKN2A (p16INK4a). On the other hand, the Zhang lab (Aird KM et al., 2015) recently showed that when cell senescence is induced by replication stress (e.g., following nucleotide deficiency), ATM inactivation allows the cell to bypass senescence by shifting cellular metabolism: upon ATM loss, dNTP levels rise due to up-regulation of the pentose phosphate pathway, whose key regulator, glucose-6-phosphate dehydrogenase (G6PD) is under functional regulation by ATM (Aird KM et al., 2015; Cosentino C et al., 2011).
  • Insulin response and lipoprotein metabolism. Other metabolic arenas in which ATM involvement is gaining attention are insulin response and lipoprotein metabolism, clinically represented by the metabolic syndrome. This role of ATM in cellular physiology was recently thoroughly and convincingly reviewed (Espach Y et al., 2015). Briefly, ATM was found to participate in several signaling pathways mediated by insulin (Yang DQ et al., 2000; Miles PD et al., 2007; Viniegra JG et al., 2005; Halaby MJ et al., 2008; Jeong I et al., 2010); and heterozygosity for Atm null allele in ApoE-deficient mice was found to aggravate their metabolic syndrome (Wu D et al., 2005; Schneider JG et al., 2006; Mercer JR et al., 2010), an effect that was partly relieved by the mitochondria-targeted antioxidant MitQ (Mercer JR et al., 2012.
  • IGF-1 receptor. Another pathway by which ATM may impact on cellular senescence is the dependence of IGF1R (IGF-1 receptor) expression on ATM (Peretz S et al., 2001; Goetz EM et al., 2011; Ching JK et al., 2013); the mechanism remains to be elucidated, but ATM impacts on IGF-1-mediated pathways, including those that affect cellular senescence (Luo X et al., 2014).
  • Beta-adrenergic receptor. Another series of observations assigned ATM a protective role in cardiac myocyte apoptosis stimulated by β-adrenergic receptor and myocardial remodeling. Loss of Atm in mice induced myocardial fibrosis and myocyte hypertrophy and interfered with cardiac remodeling following myocardial infarction (Foster CR et al., 2011; Foster CR et al., 2012; Foster CR et al., 2013; Daniel LL et al., 2014). The mechanistic aspects of these effects are still unclear, but ATM's apparent involvement in myocardial homeostasis might be relevant to the observation of elevated arteriosclerosis in A-T carriers (Swift M et al., 1983; Su Y et al., 2000).
    • Homology Phosphatidylinositol 3-kinase (PI3K)-like proteins, most closely related to ATR and the DNA-PK catalytic subunit.

    Mutations

    Note The cellular phenotype of A-T represents genome instability, deficient DNA damage response (DDR), and elevated oxidative stress, in addition to a premature senescence component (Shiloh Y et al., 1982).
    Germinal Various types of mutations have been described, dispersed throughout the gene, and therefore most patients are compound heterozygotes; most mutations appear to inactivate the ATM protein by truncation, large deletions, or annulation of initiation or termination, although missense mutations have been described in the PI3 kinase domain and the leucine zipper motif.
    Patients with the severe form of A-T are homozygous or compound heterozygous for null ATM alleles. The corresponding mutations usually lead to truncation of the ATM protein and subsequently to its loss due to instability of the truncated derivatives; a smaller portion of the mutations create amino acid substitutions that abolish ATM's catalytic activity (Taylor AM et al., 2015; Gilad S et al., 1996; Sandoval N et al., 1999; Barone G et al., 2009) (see also http://chromium.liacs.nl/LOVD2/home.php?select_db=ATM).
    Careful inspection of the neurological symptoms of A-T patients reveals variability in their age of onset and rate of progression among patients with different combinations of null ATM alleles (Taylor AM et al., 2015; Crawford TO et al., 2000; Alterman N et al., 2007). Thus, despite the identical outcome in terms of ATM function, additional genes may affect the most cardinal symptom of A-T. Other, milder types of ATM mutations further extend this variability, and account for forms of the disease with extremely variable severity and age of onset of symptoms. The corresponding ATM genotypes are combinations of hypomorphic alleles or combinations of null and hypomorphic ones. Many of the latter are leaky splicing mutations and others are missense mutations, eventually yielding low amounts of active ATM (Taylor AM et al., 2015; Alterman N et al., 2007; Soresina A et al., 2008; Verhagen MM et al., 2009; Silvestri G et al., 2010; Saunders-Pullman R et al., 2012; Verhagen MM et al., 2012; Worth PF et al., 2013; Claes K et al., 2013; Méneret A et al., 2014; Nakamura K et al., 2014; Gilad S et al., 1998).
    Somatic B A variety of missense somatic, biallelic mutations were identified in hematologic malignancies, most notably mantle cell lymphoma and T-prolymphocytic leukaemia.
    Missense mutations outside of the PI3 kinase and leucine zipper domains have been described among breast cancer patients, although these mutations have not been found in A-T patients. Whether these mutations contribute to breast cancer though not to ataxia-telangiectasia remains controversial.

    Implicated in

    Note
      
    Entity Ataxia telangiectasia
    Note Ataxia telangiectasia is a prototype genome instability syndrome (Perlman SL et al., 2012; Lavin MF, 2008; Crawford TO, 1998; Chun HH et al., 2004; Taylor AM et al., 1982; Taylor AM et al., 2015; Taylor AM, 1978; Butterworth SV et al., 1986; Kennaugh AA et al., 1986).
    Disease Ataxia telangiectasia is a progressive cerebellar degenerative disease with telangiectasia, immunodeficiency, premature aging , cancer risk, radiosensitivity, and chromosomal instability.
    Prognosis Prognosis is poor: median age at death: 17 years; survival rarely exceeds 30 years, though survival is increasing with improved medical care.
    Cytogenetics Spontaneous chromatid/chromosome breaks; non clonal stable chromosome rearrangements involving immunoglobulin superfamilly genes e.g. inv(7)(p14q35); clonal rearrangements.
      

    Bibliography

    Atm-deficient mice: a paradigm of ataxia telangiectasia.
    Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F, Shiloh Y, Crawley JN, Ried T, Tagle D, Wynshaw-Boris A
    Cell. 1996 ; 86 (1) : 159-171.
    PMID 8689683
     
    ATM-heterozygous germline mutations contribute to breast cancer-susceptibility.
    Broeks A, Urbanus JH, Floore AN, Dahler EC, Klijn JG, Rutgers EJ, Devilee P, Russell NS, van Leeuwen FE, van 't Veer LJ
    American journal of human genetics. 2000 ; 66 (2) : 494-500.
    PMID 10677309
     
    The ataxia-telangiectasia gene product, a constitutively expressed nuclear protein that is not up-regulated following genome damage.
    Brown KD, Ziv Y, Sadanandan SN, Chessa L, Collins FS, Shiloh Y, Tagle DA
    Proceedings of the National Academy of Sciences of the United States of America. 1997 ; 94 (5) : 1840-1845.
    PMID 9050866
     
    ATM phosphorylates histone H2AX in response to DNA double-strand breaks.
    Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ
    The Journal of biological chemistry. 2001 ; 276 (45) : 42462-42467.
    PMID 11571274
     
    CAND3: a ubiquitously expressed gene immediately adjacent and in opposite transcriptional orientation to the ATM gene at 11q23.1.
    Chen X, Yang L, Udar N, Liang T, Uhrhammer N, Xu S, Bay JO, Wang Z, Dandakar S, Chiplunkar S, Klisak I, Telatar M, Yang H, Concannon P, Gatti RA
    Mammalian genome : official journal of the International Mammalian Genome Society. 1997 ; 8 (2) : 129-133.
    PMID 9060412
     
    Cancer risks in A-T heterozygotes.
    Easton DF
    International journal of radiation biology. 1994 ; 66 (6 Suppl) : S177-S182.
    PMID 7836845
     
    -
    Gorlin RJ et al
    Oxford Monogr Med Genet ..
     
    TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene.
    Greenwell PW, Kronmal SL, Porter SE, Gassenhuber J, Obermaier B, Petes TD
    Cell. 1995 ; 82 (5) : 823-829.
    PMID 7671310
     
    The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene.
    Hari KL, Santerre A, Sekelsky JJ, McKim KS, Boyd JB, Hawley RS
    Cell. 1995 ; 82 (5) : 815-821.
    PMID 7671309
     
    Breast cancer risk in ataxia telangiectasia (AT) heterozygotes: haplotype study in French AT families.
    Janin N, Andrieu N, Ossian K, Laugé A, Croquette MF, Griscelli C, Debré M, Bressac-de-Paillerets B, Aurias A, Stoppa-Lyonnet D
    British journal of cancer. 1999 ; 80 (7) : 1042-1045.
    PMID 10362113
     
    Ataxia-telangiectasia locus: sequence analysis of 184 kb of human genomic DNA containing the entire ATM gene.
    Platzer M, Rotman G, Bauer D, Uziel T, Savitsky K, Bar-Shira A, Gilad S, Shiloh Y, Rosenthal A
    Genome research. 1997 ; 7 (6) : 592-605.
    PMID 9199932
     
    The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species.
    Savitsky K, Sfez S, Tagle DA, Ziv Y, Sartiel A, Collins FS, Shiloh Y, Rotman G
    Human molecular genetics. 1995 ; 4 (11) : 2025-2032.
    PMID 8589678
     
    Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart.
    Shiloh Y
    Annual review of genetics. 1997 ; 31 : 635-662.
    PMID 9442910
     
    Biallelic mutations in the ATM gene in T-prolymphocytic leukemia.
    Stilgenbauer S, Schaffner C, Litterst A, Liebisch P, Gilad S, Bar-Shira A, James MR, Lichter P, Döhner H
    Nature medicine. 1997 ; 3 (10) : 1155-1159.
    PMID 9334731
     
    Ataxia-telangiectasia: identification and detection of founder-effect mutations in the ATM gene in ethnic populations.
    Telatar M, Teraoka S, Wang Z, Chun HH, Liang T, Castellvi-Bel S, Udar N, Borresen-Dale AL, Chessa L, Bernatowska-Matuszkiewicz E, Porras O, Watanabe M, Junker A, Concannon P, Gatti RA
    American journal of human genetics. 1998 ; 62 (1) : 86-97.
    PMID 9443866
     
    Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic T-cell leukaemia.
    Vorechovský I, Luo L, Dyer MJ, Catovsky D, Amlot PL, Yaxley JC, Foroni L, Hammarström L, Webster AD, Yuille MA
    Nature genetics. 1997 ; 17 (1) : 96-99.
    PMID 9288106
     
    Cell-cycle signaling: Atm displays its many talents.
    Westphal CH
    Current biology : CB. 1997 ; 7 (12) : R789-R792.
    PMID 9382823
     
    Requirements for p53 and the ATM gene product in the regulation of G1/S and S phase checkpoints.
    Xie G, Habbersett RC, Jia Y, Peterson SR, Lehnert BE, Bradbury EM, D'Anna JA
    Oncogene. 1998 ; 16 (6) : 721-736.
    PMID 9488036
     
    ATM-related genes: what do they tell us about functions of the human gene?
    Zakian VA
    Cell. 1995 ; 82 (5) : 685-687.
    PMID 7671296
     
    Recombinant ATM protein complements the cellular A-T phenotype.
    Ziv Y, Bar-Shira A, Pecker I, Russell P, Jorgensen TJ, Tsarfati I, Shiloh Y
    Oncogene. 1997 ; 15 (2) : 159-167.
    PMID 9244351
     
    Ataxia-telangiectasia
    Perlman SL, Boder Deceased E, Sedgewick RP, Gatti RA
    Handb Clin Neurol 2012;103:307-32
    PMID 21827897
     
    Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
    Lavin MF
    Nat Rev Mol Cell Biol 2008 Oct;9(10):759-69
    PMID 18813293
     
    Ataxia telangiectasia
    Crawford TO
    Semin Pediatr Neurol 1998 Dec;5(4):287-94
    PMID 9874856
     
    Ataxia-telangiectasia, an evolving phenotype
    Chun HH, Gatti RA
    DNA Repair (Amst) 2004 Aug-Sep;3(8-9):1187-96
    PMID 15279807
     
    Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort
    Nissenkorn A, Levy-Shraga Y, Banet-Levi Y, Lahad A, Sarouk I, Modan-Moses D
    Pediatr Res 2016 Jun;79(6):889-94
    PMID 26891003
     
    Ataxia telangiectasia: more variation at clinical and cellular levels
    Taylor AM, Lam Z, Last JI, Byrd PJ
    Clin Genet 2015 Mar;87(3):199-208
    PMID 25040471
     
    Localization of an ataxia-telangiectasia gene to chromosome 11q22-23
    Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, Ersoy F, Foroud T, Jaspers NG, Lange K, et al
    Nature 1988 Dec 8;336(6199):577-80
    PMID 3200306
     
    A single ataxia telangiectasia gene with a product similar to PI-3 kinase
    Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS, Shiloh Y
    Science 1995 Jun 23;268(5218):1749-53
    PMID 7792600
     
    The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species
    Savitsky K, Sfez S, Tagle DA, Ziv Y, Sartiel A, Collins FS, Shiloh Y, Rotman G
    Hum Mol Genet 1995 Nov;4(11):2025-32
    PMID 8589678
     
    Recombinant ATM protein complements the cellular A-T phenotype
    Ziv Y, Bar-Shira A, Pecker I, Russell P, Jorgensen TJ, Tsarfati I, Shiloh Y
    Oncogene 1997 Jul 10;15(2):159-67
    PMID 9244351
     
    The ATM protein kinase: regulating the cellular response to genotoxic stress, and more
    Shiloh Y, Ziv Y
    Nat Rev Mol Cell Biol 2013 Apr;14(4):197-210
    PMID 23486281
     
    ATM: expanding roles as a chief guardian of genome stability
    Shiloh Y
    Exp Cell Res 2014 Nov 15;329(1):154-61
    PMID 25218947
     
    ATM kinase: Much more than a DNA damage responsive protein
    Guleria A, Chandna S
    DNA Repair (Amst) 2016 Mar;39:1-20
    PMID 26777338
     
    The ATM protein kinase and cellular redox signaling: beyond the DNA damage response
    Ditch S, Paull TT
    Trends Biochem Sci 2012 Jan;37(1):15-22
    PMID 22079189
     
    Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection
    BODER E, SEDGWICK RP
    Pediatrics 1958 Apr;21(4):526-54
    PMID 13542097
     
    Progressive ataxia in childhood with particular reference to ataxia-telangiectasia
    SEDGWICK RP, BODER E
    Neurology 1960 Jul;10:705-15
    PMID 14444443
     
    Ataxia-telangiectasia: an overview
    Boder E
    Kroc Found Ser 1985;19:1-63
    PMID 2415689
     
    Quantitative neurologic assessment of ataxia-telangiectasia
    Crawford TO, Mandir AS, Lefton-Greif MA, Goodman SN, Goodman BK, Sengul H, Lederman HM
    Neurology 2000 Apr 11;54(7):1505-9
    PMID 10751267
     
    Ataxia-telangiectasia
    Gatti RA
    Dermatol Clin 1995 Jan;13(1):1-6
    PMID 7712635
     
    Neuropathology in classical and variant ataxia-telangiectasia
    Verhagen MM, Martin JJ, van Deuren M, Ceuterick-de Groote C, Weemaes CM, Kremer BH, Taylor MA, Willemsen MA, Lammens M
    Neuropathology 2012 Jun;32(3):234-44
    PMID 22017321
     
    Oropharyngeal dysphagia and aspiration in patients with ataxia-telangiectasia
    Lefton-Greif MA, Crawford TO, Winkelstein JA, Loughlin GM, Koerner CB, Zahurak M, Lederman HM
    J Pediatr 2000 Feb;136(2):225-31
    PMID 10657830
     
    Bhatt JM, Bush A, van Gerven M, Nissenkorn A, Renke M, Yarlett L, Taylor M, Tonia T, Warris A, Zielen S, Zinna S, Merkus PJ; European Respiratory Society
    ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia Eur Respir Rev
    PMID 26621971
     
    Sequence of cellular events in cerebellar ontogeny relevant to expression of neuronal abnormalities in ataxia-telangiectasia
    Vinters HV, Gatti RA, Rakic P
    Kroc Found Ser 1985;19:233-55
    PMID 3864938
     
    Cerebellar pathology in ataxia-telangiectasia: the significance of basket cells
    Gatti RA, Vinters HV
    Kroc Found Ser 1985;19:225-32
    PMID 3864937
     
    Dermatologic manifestations of ataxia-telangiectasia syndrome
    Greenberger S, Berkun Y, Ben-Zeev B, Levi YB, Barziliai A, Nissenkorn A
    J Am Acad Dermatol 2013 Jun;68(6):932-6
    PMID 23360865
     
    Immunodeficiency and infections in ataxia-telangiectasia
    Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM
    J Pediatr 2004 Apr;144(4):505-11
    PMID 15069401
     
    Ataxia-Telangiectasia: a multiparameter analysis of eight families
    Gatti RA, Bick M, Tam CF, Medici MA, Oxelius VA, Holland M, Goldstein AL, Boder E
    Clin Immunol Immunopathol 1982 May;23(2):501-16
    PMID 6213343
     
    Lymphocyte subpopulations in ataxia-telangiectasia
    Weaver M, Gatti RA
    Kroc Found Ser 1985;19:309-14
    PMID 2933491
     
    DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity
    Härtlova A, Erttmann SF, Raffi FA, Schmalz AM, Resch U, Anugula S, Lienenklaus S, Nilsson LM, Kröger A, Nilsson JA, Ek T, Weiss S, Gekara NO
    Immunity 2015 Feb 17;42(2):332-43
    PMID 25692705
     
    Lymphoid malignancy as a presenting sign of ataxia-telangiectasia
    Loeb DM, Lederman HM, Winkelstein JA
    J Pediatr Hematol Oncol 2000 Sep-Oct;22(5):464-7
    PMID 11037863
     
    Malignancies in pediatric patients with ataxia telangiectasia
    Murphy RC, Berdon WE, Ruzal-Shapiro C, Hall EJ, Kornecki A, Daneman A, Brunelle F, Campbell JB
    Pediatr Radiol 1999 Apr;29(4):225-30
    PMID 10199897
     
    Cancer in patients with ataxia-telangiectasia and in their relatives in the nordic countries
    Olsen JH, Hahnemann JM, Børresen-Dale AL, Brøndum-Nielsen K, Hammarström L, Kleinerman R, Kæriäinen H, Lönnqvist T, Sankila R, Seersholm N, Tretli S, Yuen J, Boice JD Jr, Tucker M
    J Natl Cancer Inst 2001 Jan 17;93(2):121-7
    PMID 11208881
     
    Malignancy, DNA damage and chromosomal aberrations in ataxia telangiectasia
    Taylor AM, Edwards MJ
    IARC Sci Publ 1982;(39):119-26
    PMID 7152604
     
    Linear growth and endocrine function in children with ataxia telangiectasia
    Ehlayel M, Soliman A, De Sanctis V
    Indian J Endocrinol Metab 2014 Nov;18(Suppl 1):S93-6
    PMID 25538885
     
    Growth retardation and growth hormone deficiency in patients with Ataxia telangiectasia
    Voss S, Pietzner J, Hoche F, Taylor AM, Last JI, Schubert R, Zielen S
    Growth Factors 2014 Jun;32(3-4):123-9
    PMID 25060036
     
    Body composition, muscle strength and hormonal status in patients with ataxia telangiectasia: a cohort study
    Pommerening H, van Dullemen S, Kieslich M, Schubert R, Zielen S, Voss S
    Orphanet J Rare Dis 2015 Dec 9;10:155
    PMID 26645295
     
    Linear growth and endocrine function in children with ataxia telangiectasia
    Ehlayel M, Soliman A, De Sanctis V
    Indian J Endocrinol Metab 2014 Nov;18(Suppl 1):S93-6
    PMID 25538885
     
    Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort
    Nissenkorn A, Levy-Shraga Y, Banet-Levi Y, Lahad A, Sarouk I, Modan-Moses D
    Pediatr Res 2016 Jun;79(6):889-94
    PMID 26891003
     
    An unusual form of diabetes mellitus in ataxia telangiectasia
    Schalch DS, McFarlin DE, Barlow MH
    N Engl J Med 1970 Jun 18;282(25):1396-402
    PMID 4192270
     
    Diabetes mellitus in ataxia-telangiectasia, Fanconi anemia, xeroderma pigmentosum, common variable immune deficiency, and severe combined immune deficiency families
    Morrell D, Chase CL, Kupper LL, Swift M
    Diabetes 1986 Feb;35(2):143-7
    PMID 3943665
     
    Insulin-resistant diabetes mellitus in a black woman with ataxia-telangiectasia
    Blevins LS Jr, Gebhart SS
    South Med J 1996 Jun;89(6):619-21
    PMID 8638204
     
    Ataxia telangiectasia: more variation at clinical and cellular levels
    Taylor AM, Lam Z, Last JI, Byrd PJ
    Clin Genet 2015 Mar;87(3):199-208
    PMID 25040471
     
    Unrepaired DNA strand breaks in irradiated ataxia telangiectasia lymphocytes suggested from cytogenetic observations
    Taylor AM
    Mutat Res 1978 Jun;50(3):407-18
    PMID 672922
     
    A subpopulation of t(2;14)(p11;q32) cells in ataxia telangiectasia B lymphocytes
    Butterworth SV, Taylor AM
    Hum Genet 1986 Aug;73(4):346-9
    PMID 3488948
     
    The chromosome breakpoint at 14q32 in an ataxia telangiectasia t(14;14) T cell clone is different from the 14q32 breakpoint in Burkitts and an inv(14) T cell lymphoma
    Kennaugh AA, Butterworth SV, Hollis R, Baer R, Rabbitts TH, Taylor AM
    Hum Genet 1986 Jul;73(3):254-9
    PMID 3488254
     
    Ataxia telangiectasia
    Gotoff SP, Amirmokri E, Liebner EJ
    Neoplasia, untoward response to x-irradiation, and tuberous sclerosis Am J Dis Child
    PMID 6072741
     
    Radiation reaction in ataxia telangiectasia
    Morgan JL, Holcomb TM, Morrissey RW
    Am J Dis Child 1968 Nov;116(5):557-8
    PMID 5687489
     
    Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity
    Taylor AM, Harnden DG, Arlett CF, Harcourt SA, Lehmann AR, Stevens S, Bridges BA
    Nature 1975 Dec 4;258(5534):427-9
    PMID 1196376
     
    Unusual sensitivity of ataxia telangiectasia cells to bleomycin
    Taylor AM, Rosney CM, Campbell JB
    Cancer Res 1979 Mar;39(3):1046-50
    PMID 85479
     
    Cellular hypersensitivity to neocarzinostatin in ataxia-telangiectasia skin fibroblasts
    Shiloh Y, Tabor E, Becker Y
    Cancer Res 1982 Jun;42(6):2247-9
    PMID 6210429
     
    Abnormal response of ataxia-telangiectasia cells to agents that break the deoxyribose moiety of DNA via a targeted free radical mechanism
    Shiloh Y, Tabor E, Becker Y
    Carcinogenesis 1983 Oct;4(10):1317-22
    PMID 6616760
     
    Identification of ataxia telangiectasia heterozygotes, a cancer-prone population, using the single-cell gel electrophoresis (Comet) assay
    Djuzenova CS, Schindler D, Stopper H, Hoehn H, Flentje M, Oppitz U
    Lab Invest 1999 Jun;79(6):699-705
    PMID 10378512
     
    Clonal evolution of T-cell chronic lymphocytic leukaemia in a patient with ataxia telangiectasia
    Taylor AM, Butterworth SV
    Int J Cancer 1986 Apr 15;37(4):511-6
    PMID 3485581
     
    Breakage of the T cell receptor alpha chain locus in non malignant clones from patients with ataxia telangiectasia
    Heppell A, Butterworth SV, Hollis RJ, Kennaugh AA, Beatty DW, Taylor AM
    Hum Genet 1988 Aug;79(4):360-4
    PMID 2970426
     
    The cytogenetics of ataxia telangiectasia
    Kojis TL, Gatti RA, Sparkes RS
    Cancer Genet Cytogenet 1991 Oct 15;56(2):143-56
    PMID 1756458
     
    Chromosome end associations, telomeres and telomerase activity in ataxia telangiectasia cells
    Pandita TK, Pathak S, Geard CR
    Cytogenet Cell Genet 1995;71(1):86-93
    PMID 7606935
     
    Altered telomere nuclear matrix interactions and nucleosomal periodicity in ataxia telangiectasia cells before and after ionizing radiation treatment
    Smilenov LB, Dhar S, Pandita TK
    Mol Cell Biol 1999 Oct;19(10):6963-71
    PMID 10490633
     
    Characterization of ataxia telangiectasia fibroblasts with extended life-span through telomerase expression
    Wood LD, Halvorsen TL, Dhar S, Baur JA, Pandita RK, Wright WE, Hande MP, Calaf G, Hei TK, Levine F, Shay JW, Wang JJ, Pandita TK
    Oncogene 2001 Jan 18;20(3):278-88
    PMID 11313956
     
    Accelerated telomere shortening in ataxia telangiectasia
    Metcalfe JA, Parkhill J, Campbell L, Stacey M, Biggs P, Byrd PJ, Taylor AM
    Nat Genet 1996 Jul;13(3):350-3
    PMID 8673136
     
    Critical telomere shortening regulated by the ataxia-telangiectasia gene acts as a DNA damage signal leading to activation of p53 protein and limited life-span of human diploid fibroblasts
    Vaziri H
    A review Biochemistry (Mosc)
    PMID 9467855
     
    Colony-forming ability of ataxia-telangiectasia skin fibroblasts is an indicator of their early senescence and increased demand for growth factors
    Shiloh Y, Tabor E, Becker Y
    Exp Cell Res 1982 Jul;140(1):191-9
    PMID 6213420
     
    Elevated oxidative stress in patients with ataxia telangiectasia
    Reichenbach J, Schubert R, Schindler D, Müller K, Böhles H, Zielen S
    Antioxid Redox Signal 2002 Jun;4(3):465-9
    PMID 12215213
     
    Ataxia-telangiectasia: chronic activation of damage-responsive functions is reduced by alpha-lipoic acid
    Gatei M, Shkedy D, Khanna KK, Uziel T, Shiloh Y, Pandita TK, Lavin MF, Rotman G
    Oncogene 2001 Jan 18;20(3):289-94
    PMID 11313957
     
    Role of ATM in oxidative stress-mediated c-Jun phosphorylation in response to ionizing radiation and CdCl2
    Lee SA, Dritschilo A, Jung M
    J Biol Chem 2001 Apr 13;276(15):11783-90
    PMID 11278277
     
    Chromosome instability and oxidative stress markers in patients with ataxia telangiectasia and their parents
    Ludwig LB, Valiati VH, Palazzo RP, Jardim LB, da Rosa DP, Bona S, Rodrigues G, Marroni NP, Prá D, Maluf SW
    Biomed Res Int 2013;2013:762048
    PMID 23936845
     
    Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs
    Barlow C, Dennery PA, Shigenaga MK, Smith MA, Morrow JD, Roberts LJ 2nd, Wynshaw-Boris A, Levine RL
    Proc Natl Acad Sci U S A 1999 Aug 17;96(17):9915-9
    PMID 10449794
     
    Increased oxidative stress in ataxia telangiectasia evidenced by alterations in redox state of brains from Atm-deficient mice
    Kamsler A, Daily D, Hochman A, Stern N, Shiloh Y, Rotman G, Barzilai A
    Cancer Res 2001 Mar 1;61(5):1849-54
    PMID 11280737
     
    Spontaneously immortalized cell lines obtained from adult Atm null mice retain sensitivity to ionizing radiation and exhibit a mutational pattern suggestive of oxidative stress
    Gage BM, Alroy D, Shin CY, Ponomareva ON, Dhar S, Sharma GG, Pandita TK, Thayer MJ, Turker MS
    Oncogene 2001 Jul 19;20(32):4291-7
    PMID 11466609
     
    Impaired genomic stability and increased oxidative stress exacerbate different features of Ataxia-telangiectasia
    Ziv S, Brenner O, Amariglio N, Smorodinsky NI, Galron R, Carrion DV, Zhang W, Sharma GG, Pandita RK, Agarwal M, Elkon R, Katzin N, Bar-Am I, Pandita TK, Kucherlapati R, Rechavi G, Shiloh Y, Barzilai A
    Hum Mol Genet 2005 Oct 1;14(19):2929-43
    PMID 16150740
     
    Oxidative stress is responsible for deficient survival and dendritogenesis in purkinje neurons from ataxia-telangiectasia mutated mutant mice
    Chen P, Peng C, Luff J, Spring K, Watters D, Bottle S, Furuya S, Lavin MF
    J Neurosci 2003 Dec 10;23(36):11453-60
    PMID 14673010
     
    Effect of N-acetyl cysteine on oxidative DNA damage and the frequency of DNA deletions in atm-deficient mice
    Reliene R, Fischer E, Schiestl RH
    Cancer Res 2004 Aug 1;64(15):5148-53
    PMID 15289318
     
    Antioxidants suppress lymphoma and increase longevity in Atm-deficient mice
    Reliene R, Schiestl RH
    J Nutr 2007 Jan;137(1 Suppl):229S-232S
    PMID 17182831
     
    ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes
    Liu N, Stoica G, Yan M, Scofield VL, Qiang W, Lynn WS, Wong PK
    Lab Invest 2005 Dec;85(12):1471-80
    PMID 16189515
     
    Iron loading and oxidative stress in the Atm-/- mouse liver
    McDonald CJ, Ostini L, Wallace DF, John AN, Watters DJ, Subramaniam VN
    Am J Physiol Gastrointest Liver Physiol 2011 Apr;300(4):G554-60
    PMID 21292994
     
    Response of fibroblast cultures from ataxia-telangiectasia patients to oxidative stress
    Yi M, Rosin MP, Anderson CK
    Cancer Lett 1990 Oct 8;54(1-2):43-50
    PMID 2208088
     
    Response of fibroblast cultures from ataxia-telangiectasia patients to reactive oxygen species generated during inflammatory reactions
    Ward AJ, Olive PL, Burr AH, Rosin MP
    Environ Mol Mutagen 1994;24(2):103-11
    PMID 7925323
     
    Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia
    Exley AR, Buckenham S, Hodges E, Hallam R, Byrd P, Last J, Trinder C, Harris S, Screaton N, Williams AP, Taylor AM, Shneerson JM
    Clin Immunol 2011 Jul;140(1):26-36
    PMID 21459046
     
    Classical ataxia telangiectasia patients have a congenitally aged immune system with high expression of CD95
    Carney EF, Srinivasan V, Moss PA, Taylor AM
    J Immunol 2012 Jul 1;189(1):261-8
    PMID 22649200
     
    Genome instability: Linking ageing and brain degeneration
    Barzilai A, Schumacher B, Shiloh Y
    Mech Ageing Dev 2016 Mar 31
    PMID 27041231
     
    Liver Disease in Pediatric Patients With Ataxia Telangiectasia: A Novel Report
    Weiss B, Krauthammer A, Soudack M, Lahad A, Sarouk I, Somech R, Heimer G, Ben-Zeev B, Nissenkorn A
    J Pediatr Gastroenterol Nutr 2016 Apr;62(4):550-5
    PMID 26594831
     
    Oligo-/monoclonal gammopathy and hypergammaglobulinemia in ataxia-telangiectasia
    Sadighi Akha AA, Humphrey RL, Winkelstein JA, Loeb DM, Lederman HM
    A study of 90 patients Medicine (Baltimore)
    PMID 10575419
     
    Cutaneous manifestations of ataxia-telangiectasia
    Reed WB, Epstein WL, Boder E, Sedgwick R
    JAMA 1966 Feb 28;195(9):746-53
    PMID 5951880
     
    Serum Interleukin-6 Levels and Pulmonary Function in Ataxia-Telangiectasia
    McGrath-Morrow SA, Collaco JM, Detrick B, Lederman HM
    J Pediatr 2016 Apr;171:256-61
    PMID 26851119
     
    Cerebral abnormalities in adults with ataxia-telangiectasia
    Lin DD, Barker PB, Lederman HM, Crawford TO
    AJNR Am J Neuroradiol 2014 Jan;35(1):119-23
    PMID 23886747
     
    Reduced telomere length in ataxia-telangiectasia fibroblasts
    Xia SJ, Shammas MA, Shmookler Reis RJ
    Mutat Res 1996 Sep 2;364(1):1-11
    PMID 8814333
     
    Influence of ATM function on telomere metabolism
    Smilenov LB, Morgan SE, Mellado W, Sawant SG, Kastan MB, Pandita TK
    Oncogene 1997 Nov 27;15(22):2659-65
    PMID 9400992
     
    DNA repair at telomeres: keeping the ends intact
    Webb CJ, Wu Y, Zakian VA
    Cold Spring Harb Perspect Biol 2013 Jun 1;5(6)
    PMID 23732473
     
    The role of double-strand break repair pathways at functional and dysfunctional telomeres
    Doksani Y, de Lange T
    Cold Spring Harb Perspect Biol 2014 Sep 16;6(12):a016576
    PMID 25228584
     
    Complex interactions between the DNA-damage response and mammalian telomeres
    Arnoult N, Karlseder J
    Nat Struct Mol Biol 2015 Nov;22(11):859-66
    PMID 26581520
     
    Genomic Organization of the ATM gene
    Uziel T, Savitsky K, Platzer M, Ziv Y, Helbitz T, Nehls M, Boehm T, Rosenthal A, Shiloh Y, Rotman G
    Genomics 1996 Apr 15;33(2):317-20
    PMID 8660985
     
    Ataxia-telangiectasia locus: sequence analysis of 184 kb of human genomic DNA containing the entire ATM gene
    Platzer M, Rotman G, Bauer D, Uziel T, Savitsky K, Bar-Shira A, Gilad S, Shiloh Y, Rosenthal A
    Genome Res 1997 Jun;7(6):592-605
    PMID 9199932
     
    Predominance of null mutations in ataxia-telangiectasia
    Gilad S, Khosravi R, Shkedy D, Uziel T, Ziv Y, Savitsky K, Rotman G, Smith S, Chessa L, Jorgensen TJ, Harnik R, Frydman M, Sanal O, Portnoi S, Goldwicz Z, Jaspers NG, Gatti RA, Lenoir G, Lavin MF, Tatsumi K, Wegner RD, Shiloh Y, Bar-Shira A
    Hum Mol Genet 1996 Apr;5(4):433-9
    PMID 8845835
     
    Modeling ATM mutant proteins from missense changes confirms retained kinase activity
    Barone G, Groom A, Reiman A, Srinivasan V, Byrd PJ, Taylor AM
    Hum Mutat 2009 Aug;30(8):1222-30
    PMID 19431188
     
    Ataxia-telangiectasia: mild neurological presentation despite null ATM mutation and severe cellular phenotype
    Alterman N, Fattal-Valevski A, Moyal L, Crawford TO, Lederman HM, Ziv Y, Shiloh Y
    Am J Med Genet A 2007 Aug 15;143A(16):1827-34
    PMID 17632790
     
    Different clinical and immunological presentation of ataxia-telangiectasia within the same family
    Soresina A, Meini A, Lougaris V, Cattaneo G, Pellegrino S, Piane M, Darra F, Plebani A
    Neuropediatrics 2008 Feb;39(1):43-5
    PMID 18504682
     
    Clinical spectrum of ataxia-telangiectasia in adulthood
    Verhagen MM, Abdo WF, Willemsen MA, Hogervorst FB, Smeets DF, Hiel JA, Brunt ER, van Rijn MA, Majoor Krakauer D, Oldenburg RA, Broeks A, Last JI, van't Veer LJ, Tijssen MA, Dubois AM, Kremer HP, Weemaes CM, Taylor AM, van Deuren M
    Neurology 2009 Aug 11;73(6):430-7
    PMID 19535770
     
    Homozygosity for c 6325T>G transition in the ATM gene causes an atypical, late-onset variant form of ataxia-telangiectasia
    Silvestri G, Masciullo M, Piane M, Savio C, Modoni A, Santoro M, Chessa L
    J Neurol 2010 Oct;257(10):1738-40
    PMID 20480175
     
    Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites
    Saunders-Pullman R, Raymond D, Stoessl AJ, Hobson D, Nakamura K, Pullman S, Lefton D, Okun MS, Uitti R, Sachdev R, Stanley K, San Luciano M, Hagenah J, Gatti R, Ozelius LJ, Bressman SB
    Neurology 2012 Feb 28;78(9):649-57
    PMID 22345219
     
    Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: a genotype-phenotype study
    Verhagen MM, Last JI, Hogervorst FB, Smeets DF, Roeleveld N, Verheijen F, Catsman-Berrevoets CE, Wulffraat NM, Cobben JM, Hiel J, Brunt ER, Peeters EA, Gómez Garcia EB, van der Knaap MS, Lincke CR, Laan LA, Tijssen MA, van Rijn MA, Majoor-Krakauer D, Visser M, van 't Veer LJ, Kleijer WJ, van de Warrenburg BP, Warris A, de Groot IJ, de Groot R, Broeks A, Preijers F, Kremer BH, Weemaes CM, Taylor MA, van Deuren M, Willemsen MA
    Hum Mutat 2012 Mar;33(3):561-71
    PMID 22213089
     
    Very mild presentation in adult with classical cellular phenotype of ataxia telangiectasia
    Worth PF, Srinivasan V, Smith A, Last JI, Wootton LL, Biggs PM, Davies NP, Carney EF, Byrd PJ, Taylor AM
    Mov Disord 2013 Apr;28(4):524-8
    PMID 23143971
     
    Variant ataxia telangiectasia: clinical and molecular findings and evaluation of radiosensitive phenotypes in a patient and relatives
    Claes K, Depuydt J, Taylor AM, Last JI, Baert A, Schietecatte P, Vandersickel V, Poppe B, De Leeneer K, D'Hooghe M, Vral A
    Neuromolecular Med 2013 Sep;15(3):447-57
    PMID 23632773
     
    The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia
    Méneret A, Ahmar-Beaugendre Y, Rieunier G, Mahlaoui N, Gaymard B, Apartis E, Tranchant C, Rivaud-Péchoux S, Degos B, Benyahia B, Suarez F, Maisonobe T, Koenig M, Durr A, Stern MH, Dubois d'Enghien C, Fischer A, Vidailhet M, Stoppa-Lyonnet D, Grabli D, Anheim M
    Neurology 2014 Sep 16;83(12):1087-95
    PMID 25122203
     
    A-TWinnipeg: Pathogenesis of rare ATM missense mutation c
    Nakamura K, Fike F, Haghayegh S, Saunders-Pullman R, Dawson AJ, Dörk T, Gatti RA
    6200C>A with decreased protein expression and downstream signaling, early-onset dystonia, cancer, and life-threatening radiotoxicity Mol Genet Genomic Med
    PMID 25077176
     
    Genotype-phenotype relationships in ataxia-telangiectasia and variants
    Gilad S, Chessa L, Khosravi R, Russell P, Galanty Y, Piane M, Gatti RA, Jorgensen TJ, Shiloh Y, Bar-Shira A
    Am J Hum Genet 1998 Mar;62(3):551-61
    PMID 9497252
     
    ATM: expanding roles as a chief guardian of genome stability
    Shiloh Y
    Exp Cell Res 2014 Nov 15;329(1):154-61
    PMID 25218947
     
    ATM signalling and cancer
    Cremona CA, Behrens A
    Oncogene 2014 Jun 26;33(26):3351-60
    PMID 23851492
     
    Pathogenesis of ataxia-telangiectasia: the next generation of ATM functions
    Ambrose M, Gatti RA
    Blood 2013 May 16;121(20):4036-45
    PMID 23440242
     
    ATM protein kinase signaling, type 2 diabetes and cardiovascular disease
    Espach Y, Lochner A, Strijdom H, Huisamen B
    Cardiovasc Drugs Ther 2015 Feb;29(1):51-8
    PMID 25687661
     
    ATM and ATR signaling at a glance
    Awasthi P, Foiani M, Kumar A
    J Cell Sci 2016 Mar 15;129(6):1285
    PMID 26979625
     
    Common mechanisms of PIKK regulation
    Lovejoy CA, Cortez D
    DNA Repair (Amst) 2009 Sep 2;8(9):1004-8
    PMID 19464237
     
    PIKKs--the solenoid nest where partners and kinases meet
    Baretić D, Williams RL
    Curr Opin Struct Biol 2014 Dec;29:134-42
    PMID 25460276
     
    mTOR signaling for biological control and cancer
    Alayev A, Holz MK
    J Cell Physiol 2013 Aug;228(8):1658-64
    PMID 23460185
     
    mTOR in aging, metabolism, and cancer
    Cornu M, Albert V, Hall MN
    Curr Opin Genet Dev 2013 Feb;23(1):53-62
    PMID 23317514
     
    DNA-PK: a dynamic enzyme in a versatile DSB repair pathway
    Davis AJ, Chen BP, Chen DJ
    DNA Repair (Amst) 2014 May;17:21-9
    PMID 24680878
     
    The DNA-dependent protein kinase: A multifunctional protein kinase with roles in DNA double strand break repair and mitosis
    Jette N, Lees-Miller SP
    Prog Biophys Mol Biol 2015 Mar;117(2-3):194-205
    PMID 25550082
     
    Role of SMG-1-mediated Upf1 phosphorylation in mammalian nonsense-mediated mRNA decay
    Yamashita A
    Genes Cells 2013 Mar;18(3):161-75
    PMID 23356578
     
    Mechanisms of replication fork protection: a safeguard for genome stability
    Errico A, Costanzo V
    Crit Rev Biochem Mol Biol 2012 May-Jun;47(3):222-35
    PMID 22324461
     
    DNA damage sensing by the ATM and ATR kinases
    Maréchal A, Zou L
    Cold Spring Harb Perspect Biol 2013 Sep 1;5(9)
    PMID 24003211
     
    ATM and ATR signaling at a glance
    Awasthi P, Foiani M, Kumar A
    J Cell Sci 2016 Mar 15;129(6):1285
    PMID 26979625
     
    DNA damage response: three levels of DNA repair regulation
    Sirbu BM, Cortez D
    Cold Spring Harb Perspect Biol 2013 Aug 1;5(8):a012724
    PMID 23813586
     
    Recognition, signaling, and repair of DNA double-strand breaks produced by ionizing radiation in mammalian cells: the molecular choreography
    Thompson LH
    Mutat Res 2012 Oct-Dec;751(2):158-246
    PMID 22743550
     
    Interplays between ATM/Tel1 and ATR/Mec1 in sensing and signaling DNA double-strand breaks
    Gobbini E, Cesena D, Galbiati A, Lockhart A, Longhese MP
    DNA Repair (Amst) 2013 Oct;12(10):791-9
    PMID 23953933
     
    New insights into the roles of ATM and DNA-PKcs in the cellular response to oxidative stress
    Chen BP, Li M, Asaithamby A
    Cancer Lett 2012 Dec 31;327(1-2):103-10
    PMID 22155347
     
    ATM and the molecular pathogenesis of ataxia telangiectasia
    McKinnon PJ
    Annu Rev Pathol 2012;7:303-21
    PMID 22035194
     
    ROS function in redox signaling and oxidative stress
    Schieber M, Chandel NS
    Curr Biol 2014 May 19;24(10):R453-62
    PMID 24845678
     
    Programmed induction of DNA double strand breaks during meiosis: setting up communication between DNA and the chromosome structure
    Borde V, de Massy B
    Curr Opin Genet Dev 2013 Apr;23(2):147-55
    PMID 23313097
     
    ATM controls meiotic double-strand-break formation
    Lange J, Pan J, Cole F, Thelen MP, Jasin M, Keeney S
    Nature 2011 Oct 16;479(7372):237-40
    PMID 22002603
     
    Mechanisms of programmed DNA lesions and genomic instability in the immune system
    Alt FW, Zhang Y, Meng FL, Guo C, Schwer B
    Cell 2013 Jan 31;152(3):417-29
    PMID 23374339
     
    DNA double-strand break repair in a cellular context
    Shibata A, Jeggo PA
    Clin Oncol (R Coll Radiol) 2014 May;26(5):243-9
    PMID 24630811
     
    Playing the end game: DNA double-strand break repair pathway choice
    Chapman JR, Taylor MR, Boulton SJ
    Mol Cell 2012 Aug 24;47(4):497-510
    PMID 22920291
     
    Repair of strand breaks by homologous recombination
    Jasin M, Rothstein R
    Cold Spring Harb Perspect Biol 2013 Nov 1;5(11):a012740
    PMID 24097900
     
    Non-homologous end joining: emerging themes and unanswered questions
    Radhakrishnan SK, Jette N, Lees-Miller SP
    DNA Repair (Amst) 2014 May;17:2-8
    PMID 24582502
     
    The repair and signaling responses to DNA double-strand breaks
    Goodarzi AA, Jeggo PA
    Adv Genet 2013;82:1-45
    PMID 23721719
     
    Push back to respond better: regulatory inhibition of the DNA double-strand break response
    Panier S, Durocher D
    Nat Rev Mol Cell Biol 2013 Oct;14(10):661-72
    PMID 24002223
     
    Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications
    Polo SE, Jackson SP
    Genes Dev 2011 Mar 1;25(5):409-33
    PMID 21363960
     
    The ATM protein kinase: regulating the cellular response to genotoxic stress, and more
    Shiloh Y, Ziv Y
    Nat Rev Mol Cell Biol 2013 Apr;14(4):197-210
    PMID 23486281
     
    ATM protein kinase: the linchpin of cellular defenses to stress
    Bhatti S, Kozlov S, Farooqi AA, Naqi A, Lavin M, Khanna KK
    Cell Mol Life Sci 2011 Sep;68(18):2977-3006
    PMID 21533982
     
    DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
    Bakkenist CJ, Kastan MB
    Nature 2003 Jan 30;421(6922):499-506
    PMID 12556884
     
    Involvement of novel autophosphorylation sites in ATM activation
    Kozlov SV, Graham ME, Peng C, Chen P, Robinson PJ, Lavin MF
    EMBO J 2006 Aug 9;25(15):3504-14
    PMID 16858402
     
    ATM-dependent and -independent dynamics of the nuclear phosphoproteome after DNA damage
    Bensimon A, Schmidt A, Ziv Y, Elkon R, Wang SY, Chen DJ, Aebersold R, Shiloh Y
    Sci Signal 2010 Dec 7;3(151):rs3
    PMID 21139141
     
    DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase activity
    Sun Y, Xu Y, Roy K, Price BD
    Mol Cell Biol 2007 Dec;27(24):8502-9
    PMID 17923702
     
    KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling
    Kaidi A, Jackson SP
    Nature 2013 Jun 6;498(7452):70-4
    PMID 23708966
     
    Mechanisms of ATM Activation
    Paull TT
    Annu Rev Biochem 2015;84:711-38
    PMID 25580527
     
    ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
    Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ
    Science 2007 May 25;316(5828):1160-6
    PMID 17525332
     
    A proteomic analysis of ataxia telangiectasia-mutated (ATM)/ATM-Rad3-related (ATR) substrates identifies the ubiquitin-proteasome system as a regulator for DNA damage checkpoints
    Mu JJ, Wang Y, Luo H, Leng M, Zhang J, Yang T, Besusso D, Jung SY, Qin J
    J Biol Chem 2007 Jun 15;282(24):17330-4
    PMID 17478428
     
    Beyond ATM: the protein kinase landscape of the DNA damage response
    Bensimon A, Aebersold R, Shiloh Y
    FEBS Lett 2011 Jun 6;585(11):1625-39
    PMID 21570395
     
    ATM prevents DSB formation by coordinating SSB repair and cell cycle progression
    Khoronenkova SV, Dianov GL
    Proc Natl Acad Sci U S A 2015 Mar 31;112(13):3997-4002
    PMID 25775545
     
    Base excision repair: a critical player in many games
    Wallace SS
    DNA Repair (Amst) 2014 Jul;19:14-26
    PMID 24780558
     
    The current state of eukaryotic DNA base damage and repair
    Bauer NC, Corbett AH, Doetsch PW
    Nucleic Acids Res 2015 Dec 2;43(21):10083-101
    PMID 26519467
     
    ATM-mediated phosphorylation of polynucleotide kinase/phosphatase is required for effective DNA double-strand break repair
    Segal-Raz H, Mass G, Baranes-Bachar K, Lerenthal Y, Wang SY, Chung YM, Ziv-Lehrman S, Ström CE, Helleday T, Hu MC, Chen DJ, Shiloh Y
    EMBO Rep 2011 Jul 1;12(7):713-9
    PMID 21637298
     
    Phosphorylation of polynucleotide kinase/ phosphatase by DNA-dependent protein kinase and ataxia-telangiectasia mutated regulates its association with sites of DNA damage
    Zolner AE, Abdou I, Ye R, Mani RS, Fanta M, Yu Y, Douglas P, Tahbaz N, Fang S, Dobbs T, Wang C, Morrice N, Hendzel MJ, Weinfeld M, Lees-Miller SP
    Nucleic Acids Res 2011 Nov;39(21):9224-37
    PMID 21824916
     
    Chemical mutagen hypersensitivity in ataxia telangiectasia
    Hoar DI, Sargent P
    Nature 1976 Jun 17;261(5561):590-2
    PMID 180416
     
    Defective excision repair of gamma-ray-damaged DNA in human (ataxia telangiectasia) fibroblasts
    Paterson MC, Smith BP, Lohman PH, Anderson AK, Fishman L
    Nature 1976 Apr 1;260(5550):444-7
    PMID 1256588
     
    Defective DNA repair and increased lethality in ataxia telangiectasia cells exposed to 4-nitroquinoline-1-oxide
    Smith PJ, Paterson MC
    Nature 1980 Oct 23;287(5784):747-9
    PMID 6776412
     
    Hypersensitivity to cell killing and faulty repair of 1-beta-D-arabinofuranosylcytosine-detectable sites in human (ataxia-telangiectasia) fibroblasts treated with 4-nitroquinoline 1-oxide
    Mirzayans R, Smith BP, Paterson MC
    Cancer Res 1989 Oct 15;49(20):5523-9
    PMID 2507129
     
    DNA repair in lymphoblastoid cell lines established from human genetic disorders
    Henderson EE, Ribecky R
    Chem Biol Interact 1980 Dec;33(1):63-81
    PMID 7438293
     
    Decreased DNA repair synthesis and defective colony-forming ability of ataxia telangiectasia fibroblast cell strains treated with N-methyl-N'-nitro-N-nitrosoguanidine
    Scudiero DA
    Cancer Res 1980 Apr;40(4):984-90
    PMID 7357564
     
    Abnormal regulation of DNA replication and increased lethality in ataxia telangiectasia cells exposed to carcinogenic agents
    Jaspers NG, de Wit J, Regulski MR, Bootsma D
    Cancer Res 1982 Jan;42(1):335-41
    PMID 6172195
     
    The response of a variety of human fibroblast cell strains to the lethal effects of alkylating agents
    Teo IA, Arlett CF
    Carcinogenesis 1982;3(1):33-7
    PMID 7067035
     
    Hypersensitivity of ataxia telangiectasia skin fibroblasts to DNA alkylating agents
    Barfknecht TR, Little JB
    Mutat Res 1982 Jun;94(2):369-82
    PMID 6810166
     
    Loss of atm sensitises p53-deficient cells to topoisomerase poisons and antimetabolites
    Fedier A, Schlamminger M, Schwarz VA, Haller U, Howell SB, Fink D
    Ann Oncol 2003 Jun;14(6):938-45
    PMID 12796033
     
    Genome instability in ataxia telangiectasia (A-T) families: camptothecin-induced damage to replicating DNA discriminates between obligate A-T heterozygotes, A-T homozygotes and controls
    Leonard JC, Mullinger AM, Schmidt J, Cordell HJ, Johnson RT
    Biosci Rep 2004 Dec;24(6):617-29
    PMID 16158199
     
    Ataxia-telangiectasia-mutated-dependent activation of Ku in human fibroblasts exposed to hydrogen peroxide
    Lee JH, Kim KH, Morio T, Kim H
    Ann N Y Acad Sci 2006 Dec;1091:76-82
    PMID 17341604
     
    Induction of p53 and increased sensitivity to cisplatin in ataxia-telangiectasia cells
    Zhang N, Song Q, Lu H, Lavin MF
    Oncogene 1996 Aug 1;13(3):655-9
    PMID 8760308
     
    Enhanced sensitivity to camptothecin in ataxia-telangiectasia cells and its relationship with the expression of DNA topoisomerase I
    Smith PJ, Makinson TA, Watson JV
    Int J Radiat Biol 1989 Feb;55(2):217-31
    PMID 2563396
     
    ATM deficiency results in accumulation of DNA-topoisomerase I covalent intermediates in neural cells
    Alagoz M, Chiang SC, Sharma A, El-Khamisy SF
    PLoS One 2013;8(4):e58239
    PMID 23626666
     
    Aberrant topoisomerase-1 DNA lesions are pathogenic in neurodegenerative genome instability syndromes
    Katyal S, Lee Y, Nitiss KC, Downing SM, Li Y, Shimada M, Zhao J, Russell HR, Petrini JH, Nitiss JL, McKinnon PJ
    Nat Neurosci 2014 Jun;17(6):813-21
    PMID 24793032
     
    Mutagen sensitivity of human lymphoblastoid cells with a BRCA1 mutation in comparison to ataxia telangiectasia heterozygote cells
    Speit G, Trenz K, Schütz P, Bendix R, Dörk T
    Cytogenet Cell Genet 2000;91(1-4):261-6
    PMID 11173867
     
    Cells from patients with ataxia telangiectasia are abnormally sensitive to the cytotoxic effect of a tumor promoter, phorbol-12-myristate-13-acetate
    Shiloh Y, Tabor E, Becker Y
    Mutat Res 1985 Apr;149(2):283-6
    PMID 3982447
     
    Deficiency in the repair of UV-induced DNA damage in human skin fibroblasts compromised for the ATM gene
    Hannan MA, Hellani A, Al-Khodairy FM, Kunhi M, Siddiqui Y, Al-Yussef N, Pangue-Cruz N, Siewertsen M, Al-Ahdal MN, Aboussekhra A
    Carcinogenesis 2002 Oct;23(10):1617-24
    PMID 12376469
     
    Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia
    Li J, Chen J, Ricupero CL, Hart RP, Schwartz MS, Kusnecov A, Herrup K
    Nat Med 2012 May;18(5):783-90
    PMID 22466704
     
    The role of ATM and DNA damage in neurons: upstream and downstream connections
    Herrup K, Li J, Chen J
    DNA Repair (Amst) 2013 Aug;12(8):600-4
    PMID 23680599
     
    ATM and the epigenetics of the neuronal genome
    Herrup K
    Mech Ageing Dev 2013 Oct;134(10):434-9
    PMID 23707635
     
    EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia
    Li J, Hart RP, Mallimo EM, Swerdel MR, Kusnecov AW, Herrup K
    Nat Neurosci 2013 Dec;16(12):1745-53
    PMID 24162653
     
    Alteration in 5-hydroxymethylcytosine-mediated epigenetic regulation leads to Purkinje cell vulnerability in ATM deficiency
    Jiang D, Zhang Y, Hart RP, Chen J, Herrup K, Li J
    Brain 2015 Dec;138(Pt 12):3520-36
    PMID 26510954
     
    Localization of a portion of extranuclear ATM to peroxisomes
    Watters D, Kedar P, Spring K, Bjorkman J, Chen P, Gatei M, Birrell G, Garrone B, Srinivasa P, Crane DI, Lavin MF
    J Biol Chem 1999 Nov 26;274(48):34277-82
    PMID 10567403
     
    The peroxisome as a cell signaling organelle
    Tripathi DN, Walker CL
    Curr Opin Cell Biol 2016 Apr;39:109-12
    PMID 26967755
     
    ATM functions at the peroxisome to induce pexophagy in response to ROS
    Zhang J, Tripathi DN, Jing J, Alexander A, Kim J, Powell RT, Dere R, Tait-Mulder J, Lee JH, Paull TT, Pandita RK, Charaka VK, Pandita TK, Kastan MB, Walker CL
    Nat Cell Biol 2015 Oct;17(10):1259-69
    PMID 26344566
     
    Mitochondrial dysfunction in ataxia-telangiectasia
    Valentin-Vega YA, Maclean KH, Tait-Mulder J, Milasta S, Steeves M, Dorsey FC, Cleveland JL, Green DR, Kastan MB
    Blood 2012 Feb 9;119(6):1490-500
    PMID 22144182
     
    Ataxia-telangiectasia: is ATM a sensor of oxidative damage and stress? Bioessays
    Rotman G, Shiloh Y
    1997 Oct;19(10):911-7 Review
    PMID 9363685
     
    The ATM gene and protein: possible roles in genome surveillance, checkpoint controls and cellular defence against oxidative stress
    Rotman G, Shiloh Y
    Cancer Surv 1997;29:285-304
    PMID 9338105
     
    ATM deficiency and oxidative stress: a new dimension of defective response to DNA damage
    Barzilai A, Rotman G, Shiloh Y
    DNA Repair (Amst) 2002 Jan 22;1(1):3-25
    PMID 12509294
     
    Oxidative stress in ataxia telangiectasia
    Watters DJ
    Redox Rep 2003;8(1):23-9
    PMID 12631440
     
    Protective roles for ATM in cellular response to oxidative stress
    Takao N, Li Y, Yamamoto K
    FEBS Lett 2000 Apr 21;472(1):133-6
    PMID 10781820
     
    ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS
    Alexander A, Cai SL, Kim J, Nanez A, Sahin M, MacLean KH, Inoki K, Guan KL, Shen J, Person MD, Kusewitt D, Mills GB, Kastan MB, Walker CL
    Proc Natl Acad Sci U S A 2010 Mar 2;107(9):4153-8
    PMID 20160076
     
    ATM activation by oxidative stress
    Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT
    Science 2010 Oct 22;330(6003):517-21
    PMID 20966255
     
    ATM activation in the presence of oxidative stress
    Guo Z, Deshpande R, Paull TT
    Cell Cycle 2010 Dec 15;9(24):4805-11
    PMID 21150274
     
    Direct activation of ATM by resveratrol under oxidizing conditions
    Lee JH, Guo Z, Myler LR, Zheng S, Paull TT
    PLoS One 2014 Jun 16;9(6):e97969
    PMID 24933654
     
    ATM protects against oxidative stress induced by oxidized low-density lipoprotein
    Semlitsch M, Shackelford RE, Zirkl S, Sattler W, Malle E
    DNA Repair (Amst) 2011 Aug 15;10(8):848-60
    PMID 21669554
     
    ATM is a redox sensor linking genome stability and carbon metabolism
    Krüger A, Ralser M
    Sci Signal 2011 Apr 5;4(167):pe17
    PMID 21467295
     
    Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen
    Kozlov SV, Waardenberg AJ, Engholm-Keller K, Arthur JW, Graham ME, Lavin M
    Mol Cell Proteomics 2016 Mar;15(3):1032-47
    PMID 26699800
     
    Reactive nitrogen species regulate autophagy through ATM-AMPK-TSC2-mediated suppression of mTORC1
    Tripathi DN, Chowdhury R, Trudel LJ, Tee AR, Slack RS, Walker CL, Wogan GN
    Proc Natl Acad Sci U S A 2013 Aug 6;110(32):E2950-7
    PMID 23878245
     
    A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1 and autophagy in response to ROS
    Zhang J, Kim J, Alexander A, Cai S, Tripathi DN, Dere R, Tee AR, Tait-Mulder J, Di Nardo A, Han JM, Kwiatkowski E, Dunlop EA, Dodd KM, Folkerth RD, Faust PL, Kastan MB, Sahin M, Walker CL
    Nat Cell Biol 2013 Oct;15(10):1186-96
    PMID 23955302
     
    ATM engages the TSC2/mTORC1 signaling node to regulate autophagy
    Alexander A, Kim J, Walker CL
    Autophagy 2010 Jul;6(5):672-3
    PMID 20581436
     
    Differential localization of ATM is correlated with activation of distinct downstream signaling pathways
    Alexander A, Walker CL
    Cell Cycle 2010 Sep 15;9(18):3685-6
    PMID 20890104
     
    Pexophagy: the selective degradation of peroxisomes
    Till A, Lakhani R, Burnett SF, Subramani S
    Int J Cell Biol 2012;2012:512721
    PMID 22536249
     
    Intrinsic mitochondrial dysfunction in ATM-deficient lymphoblastoid cells
    Ambrose M, Goldstine JV, Gatti RA
    Hum Mol Genet 2007 Sep 15;16(18):2154-64
    PMID 17606465
     
    Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis
    Eaton JS, Lin ZP, Sartorelli AC, Bonawitz ND, Shadel GS
    J Clin Invest 2007 Sep;117(9):2723-34
    PMID 17786248
     
    Etoposide induces ATM-dependent mitochondrial biogenesis through AMPK activation
    Fu X, Wan S, Lyu YL, Liu LF, Qi H
    PLoS One 2008 Apr 23;3(4):e2009
    PMID 18431490
     
    A new role for ATM: regulating mitochondrial function and mitophagy
    Valentin-Vega YA, Kastan MB
    Autophagy 2012 May 1;8(5):840-1
    PMID 22617444
     
    Reducing mitochondrial ROS improves disease-related pathology in a mouse model of ataxia-telangiectasia
    D'Souza AD, Parish IA, Krause DS, Kaech SM, Shadel GS
    Mol Ther 2013 Jan;21(1):42-8
    PMID 23011031
     
    Intrinsic mitochondrial DNA repair defects in Ataxia Telangiectasia
    Sharma NK, Lebedeva M, Thomas T, Kovalenko OA, Stumpf JD, Shadel GS, Santos JH
    DNA Repair (Amst) 2014 Jan;13:22-31
    PMID 24342190
     
    MacroH2A1 and ATM Play Opposing Roles in Paracrine Senescence and the Senescence-Associated Secretory Phenotype
    Chen H, Ruiz PD, McKimpson WM, Novikov L, Kitsis RN, Gamble MJ
    Mol Cell 2015 Sep 3;59(5):719-31
    PMID 26300260
     
    The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4
    Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, Lu T, Yankner BA, Campisi J, Elledge SJ
    Science 2015 Sep 25;349(6255):aaa5612
    PMID 26404840
     
    ATM couples replication stress and metabolic reprogramming during cellular senescence
    Aird KM, Worth AJ, Snyder NW, Lee JV, Sivanand S, Liu Q, Blair IA, Wellen KE, Zhang R
    Cell Rep 2015 May 12;11(6):893-901
    PMID 25937285
     
    ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair
    Cosentino C, Grieco D, Costanzo V
    EMBO J 2011 Feb 2;30(3):546-55
    PMID 21157431
     
    Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1
    Yang DQ, Kastan MB
    Nat Cell Biol 2000 Dec;2(12):893-8
    PMID 11146653
     
    Impaired insulin secretion in a mouse model of ataxia telangiectasia
    Miles PD, Treuner K, Latronica M, Olefsky JM, Barlow C
    Am J Physiol Endocrinol Metab 2007 Jul;293(1):E70-4
    PMID 17356010
     
    Full activation of PKB/Akt in response to insulin or ionizing radiation is mediated through ATM
    Viniegra JG, Martínez N, Modirassari P, Hernández Losa J, Parada Cobo C, Sánchez-Arévalo Lobo VJ, Aceves Luquero CI, Alvarez-Vallina L, Ramón y Cajal S, Rojas JM, Sánchez-Prieto R
    J Biol Chem 2005 Feb 11;280(6):4029-36
    PMID 15546863
     
    ATM protein kinase mediates full activation of Akt and regulates glucose transporter 4 translocation by insulin in muscle cells
    Halaby MJ, Hibma JC, He J, Yang DQ
    Cell Signal 2008 Aug;20(8):1555-63
    PMID 18534819
     
    Role of ataxia telangiectasia mutated in insulin signalling of muscle-derived cell lines and mouse soleus
    Jeong I, Patel AY, Zhang Z, Patil PB, Nadella ST, Nair S, Ralston L, Hoormann JK, Fisher JS
    Acta Physiol (Oxf) 2010 Apr;198(4):465-75
    PMID 20003097
     
    Heterozygous mutation of ataxia-telangiectasia mutated gene aggravates hypercholesterolemia in apoE-deficient mice
    Wu D, Yang H, Xiang W, Zhou L, Shi M, Julies G, Laplante JM, Ballard BR, Guo Z
    J Lipid Res 2005 Jul;46(7):1380-7
    PMID 15863839
     
    ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome
    Schneider JG, Finck BN, Ren J, Standley KN, Takagi M, Maclean KH, Bernal-Mizrachi C, Muslin AJ, Kastan MB, Semenkovich CF
    Cell Metab 2006 Nov;4(5):377-89
    PMID 17084711
     
    DNA damage links mitochondrial dysfunction to atherosclerosis and the metabolic syndrome
    Mercer JR, Cheng KK, Figg N, Gorenne I, Mahmoudi M, Griffin J, Vidal-Puig A, Logan A, Murphy MP, Bennett M
    Circ Res 2010 Oct 15;107(8):1021-31
    PMID 20705925
     
    The mitochondria-targeted antioxidant MitoQ decreases features of the metabolic syndrome in ATM+/-/ApoE-/- mice
    Mercer JR, Yu E, Figg N, Cheng KK, Prime TA, Griffin JL, Masoodi M, Vidal-Puig A, Murphy MP, Bennett MR
    Free Radic Biol Med 2012 Mar 1;52(5):841-9
    PMID 22210379
     
    ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response
    Peretz S, Jensen R, Baserga R, Glazer PM
    Proc Natl Acad Sci U S A 2001 Feb 13;98(4):1676-81
    PMID 11172010
     
    ATM-dependent IGF-1 induction regulates secretory clusterin expression after DNA damage and in genetic instability
    Goetz EM, Shankar B, Zou Y, Morales JC, Luo X, Araki S, Bachoo R, Mayo LD, Boothman DA
    Oncogene 2011 Sep 1;30(35):3745-54
    PMID 21460853
     
    Ataxia telangiectasia mutated impacts insulin-like growth factor 1 signalling in skeletal muscle
    Ching JK, Luebbert SH, Collins RL 4th, Zhang Z, Marupudi N, Banerjee S, Hurd RD, Ralston L, Fisher JS
    Exp Physiol 2013 Feb;98(2):526-35
    PMID 22941977
     
    ATM regulates insulin-like growth factor 1-secretory clusterin (IGF-1-sCLU) expression that protects cells against senescence
    Luo X, Suzuki M, Ghandhi SA, Amundson SA, Boothman DA
    PLoS One 2014 Jun 17;9(6):e99983
    PMID 24937130
     
    Ataxia telangiectasia mutated kinase plays a protective role in β-adrenergic receptor-stimulated cardiac myocyte apoptosis and myocardial remodeling
    Foster CR, Singh M, Subramanian V, Singh K
    Mol Cell Biochem 2011 Jul;353(1-2):13-22
    PMID 21404020
     
    Lack of ataxia telangiectasia mutated kinase induces structural and functional changes in the heart: role in β-adrenergic receptor-stimulated apoptosis
    Foster CR, Zha Q, Daniel LL, Singh M, Singh K
    Exp Physiol 2012 Apr;97(4):506-15
    PMID 22179422
     
    Deficiency of ataxia telangiectasia mutated kinase modulates cardiac remodeling following myocardial infarction: involvement in fibrosis and apoptosis
    Foster CR, Daniel LL, Daniels CR, Dalal S, Singh M, Singh K
    PLoS One 2013 Dec 16;8(12):e83513
    PMID 24358288
     
    Deficiency of ataxia telangiectasia mutated kinase delays inflammatory response in the heart following myocardial infarction
    Daniel LL, Daniels CR, Harirforoosh S, Foster CR, Singh M, Singh K
    J Am Heart Assoc 2014 Dec;3(6):e001286
    PMID 25520329
     
    Cancer and cardiac deaths in obligatory ataxia-telangiectasia heterozygotes
    Swift M, Chase C
    Lancet 1983 May 7;1(8332):1049-50
    PMID 6133091
     
    Mortality rates among carriers of ataxia-telangiectasia mutant alleles
    Su Y, Swift M
    Ann Intern Med 2000 Nov 21;133(10):770-8
    PMID 11085839
     

    Citation

    This paper should be referenced as such :
    Shiloh Y
    ATM (ataxia telangiectasia mutated);
    Atlas Genet Cytogenet Oncol Haematol. in press
    On line version : http://AtlasGeneticsOncology.org/Genes/ATMID123.html
    History of this paper:
    Huret, JL. ATM (ataxia telangiectasia mutated). Atlas Genet Cytogenet Oncol Haematol. 1998;2(3):77-78.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37430/04-1998-ATM123.pdf
    Uhrhammer, N ; Bay, JO ; Gatti, RA. ATM (ataxia telangiectasia mutated). Atlas Genet Cytogenet Oncol Haematol. 1999;3(4):173-174.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37550/10-1999-ATM123.pdf
    Uhrhammer, N ; Bay, JO ; Gatti, RA. ATM (ataxia telangiectasia mutated). Atlas Genet Cytogenet Oncol Haematol. 2003;7(1):12-13.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37923/11-2002-ATM123.pdf

    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 24 ]
      Classification of B-cell chronic lymphoproliferative disorders (CLD)
    Chronic lymphocytic leukaemia (CLL)
    Chronic myelogenous leukaemia (CML)
    del(11q) in non-Hodgkin's lymphoma (NHL)
    dic(9;17)(p13;q11) PAX5/TAOK1
    Small lymphocytic lymphoma
    t(1;3)(q25;q27) GAS5/BCL6
    t(3;3)(q27;q27) ST6GAL1/BCL6::del(3)(q27q27) ST6GAL1/BCL6
    t(3;6)(q27;p22) HIST1H4I/BCL6
    t(3;6)(q27;q14) SNHG5/BCL6
    t(3;6)(q27;q15) ?/BCL6
    t(3;7)(q27;q32) FRA7H/BCL6
    t(3;9)(q27;p13) GRHPR/BCL6
    t(3;9)(q27;p24) DMRT1/BCL6
    t(3;11)(q27;q23) POU2AF1/BCL6
    t(3;12)(q27;p12) LRMP/BCL6
    t(3;14)(q27;q32) HSP90AA1/BCL6
    t(3;19)(q27;q13) NAPA/BCL6
    t(6;9)(p22;q34) DEK/NUP214
    t(6;9)(p22;q34) DEK/NUP214 in Childhood
    Classification of T-Cell disorders
    T-cell/histiocyte rich large B-cell lymphoma
    T-cell prolymphocytic leukemia (T-PLL)
    t(X;14)(q28;q11.2) TRA-TRD/MTCP1::t(X;7)(q28;q34) TRB/MTCP1

    Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ]
      Breast tumors : an overview
    Breast: Ductal carcinoma
    Male breast cancer
    Pancreatic tumors: an overview

    Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 2 ]
      Ataxia telangiectasia (A-T) Hereditary breast cancer

    External links

    Nomenclature
    HGNC (Hugo)ATM   795
    LRG (Locus Reference Genomic)LRG_135
    Cards
    AtlasATMID123
    Entrez_Gene (NCBI)ATM  472  ATM serine/threonine kinase
    AliasesAT1; ATA; ATC; ATD; 
    ATDC; ATE; TEL1; TELO1
    GeneCards (Weizmann)ATM
    Ensembl hg19 (Hinxton)ENSG00000149311 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000149311 [Gene_View]  chr11:108222832-108369099 [Contig_View]  ATM [Vega]
    ICGC DataPortalENSG00000149311
    TCGA cBioPortalATM
    AceView (NCBI)ATM
    Genatlas (Paris)ATM
    WikiGenes472
    SOURCE (Princeton)ATM
    Genetics Home Reference (NIH)ATM
    Genomic and cartography
    GoldenPath hg38 (UCSC)ATM  -     chr11:108222832-108369099 +  11q22.3   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)ATM  -     11q22.3   [Description]    (hg19-Feb_2009)
    EnsemblATM - 11q22.3 [CytoView hg19]  ATM - 11q22.3 [CytoView hg38]
    Mapping of homologs : NCBIATM [Mapview hg19]  ATM [Mapview hg38]
    OMIM114480   208900   607585   
    Gene and transcription
    Genbank (Entrez)AB209133 AF035326 AF035327 AF035328 AK299843
    RefSeq transcript (Entrez)NM_000051 NM_138292 NM_138293
    RefSeq genomic (Entrez)
    Consensus coding sequences : CCDS (NCBI)ATM
    Cluster EST : UnigeneHs.367437 [ NCBI ]
    CGAP (NCI)Hs.367437
    Alternative Splicing GalleryENSG00000149311
    Gene ExpressionATM [ NCBI-GEO ]   ATM [ EBI - ARRAY_EXPRESS ]   ATM [ SEEK ]   ATM [ MEM ]
    Gene Expression Viewer (FireBrowse)ATM [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)472
    GTEX Portal (Tissue expression)ATM
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ13315   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtQ13315  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ13315
    Splice isoforms : SwissVarQ13315
    Catalytic activity : Enzyme2.7.11.1 [ Enzyme-Expasy ]   2.7.11.12.7.11.1 [ IntEnz-EBI ]   2.7.11.1 [ BRENDA ]   2.7.11.1 [ KEGG ]   
    PhosPhoSitePlusQ13315
    Domaine pattern : Prosite (Expaxy)FAT (PS51189)    FATC (PS51190)    PI3_4_KINASE_1 (PS00915)    PI3_4_KINASE_2 (PS00916)    PI3_4_KINASE_3 (PS50290)   
    Domains : Interpro (EBI)ARM-type_fold    FATC_dom    Kinase-like_dom    PI3/4_kinase_cat_dom    PI3/4_kinase_CS    PIK-rel_kinase_FAT    PIK_FAT    TAN   
    Domain families : Pfam (Sanger)FAT (PF02259)    FATC (PF02260)    PI3_PI4_kinase (PF00454)    TAN (PF11640)   
    Domain families : Pfam (NCBI)pfam02259    pfam02260    pfam00454    pfam11640   
    Domain families : Smart (EMBL)FATC (SM01343)  PI3Kc (SM00146)  TAN (SM01342)  
    Conserved Domain (NCBI)ATM
    DMDM Disease mutations472
    Blocks (Seattle)ATM
    SuperfamilyQ13315
    Human Protein AtlasENSG00000149311
    Peptide AtlasQ13315
    HPRD06347
    IPIIPI00298306   IPI00783886   IPI00816070   IPI00930438   IPI00977827   IPI00976048   IPI00977195   IPI00976623   IPI00977797   IPI00979647   
    Protein Interaction databases
    DIP (DOE-UCLA)Q13315
    IntAct (EBI)Q13315
    FunCoupENSG00000149311
    BioGRIDATM
    STRING (EMBL)ATM
    ZODIACATM
    Ontologies - Pathways
    QuickGOQ13315
    Ontology : AmiGOdouble-strand break repair via homologous recombination  DNA double-strand break processing  DNA synthesis involved in DNA repair  strand displacement  chromosome, telomeric region  nuclear chromosome, telomeric region  ovarian follicle development  response to hypoxia  somitogenesis  pre-B cell allelic exclusion  immunoglobulin production  DNA binding  protein serine/threonine kinase activity  protein serine/threonine kinase activity  DNA-dependent protein kinase activity  protein binding  ATP binding  nucleus  nucleoplasm  spindle  DNA replication  double-strand break repair via nonhomologous end joining  protein phosphorylation  protein phosphorylation  cellular response to DNA damage stimulus  cellular response to DNA damage stimulus  DNA damage induced protein phosphorylation  DNA damage induced protein phosphorylation  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  cell cycle arrest  mitotic spindle assembly checkpoint  reciprocal meiotic recombination  male meiotic nuclear division  female meiotic nuclear division  signal transduction  brain development  heart development  determination of adult lifespan  intrinsic apoptotic signaling pathway in response to DNA damage  post-embryonic development  response to ionizing radiation  regulation of autophagy  1-phosphatidylinositol-3-kinase activity  peptidyl-serine phosphorylation  negative regulation of B cell proliferation  cytoplasmic vesicle  regulation of telomere maintenance via telomerase  positive regulation of telomere maintenance via telomerase  protein complex binding  positive regulation of histone phosphorylation  V(D)J recombination  multicellular organism growth  phosphatidylinositol-3-phosphate biosynthetic process  peptidyl-serine autophosphorylation  lipoprotein catabolic process  regulation of apoptotic process  positive regulation of apoptotic process  positive regulation of DNA damage response, signal transduction by p53 class mediator  positive regulation of neuron apoptotic process  meiotic telomere clustering  protein autophosphorylation  protein autophosphorylation  protein dimerization activity  protein N-terminus binding  thymus development  oocyte development  neuron apoptotic process  regulation of telomerase activity  histone mRNA catabolic process  cellular response to gamma radiation  cellular response to X-ray  cellular response to nitrosative stress  signal transduction involved in mitotic G2 DNA damage checkpoint  replicative senescence  establishment of RNA localization to telomere  establishment of macromolecular complex localization to telomere  regulation of cellular response to heat  regulation of signal transduction by p53 class mediator  negative regulation of TORC1 signaling  negative regulation of telomere capping  positive regulation of telomere maintenance via telomere lengthening  positive regulation of telomerase catalytic core complex assembly  DNA repair complex  
    Ontology : EGO-EBIdouble-strand break repair via homologous recombination  DNA double-strand break processing  DNA synthesis involved in DNA repair  strand displacement  chromosome, telomeric region  nuclear chromosome, telomeric region  ovarian follicle development  response to hypoxia  somitogenesis  pre-B cell allelic exclusion  immunoglobulin production  DNA binding  protein serine/threonine kinase activity  protein serine/threonine kinase activity  DNA-dependent protein kinase activity  protein binding  ATP binding  nucleus  nucleoplasm  spindle  DNA replication  double-strand break repair via nonhomologous end joining  protein phosphorylation  protein phosphorylation  cellular response to DNA damage stimulus  cellular response to DNA damage stimulus  DNA damage induced protein phosphorylation  DNA damage induced protein phosphorylation  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  cell cycle arrest  mitotic spindle assembly checkpoint  reciprocal meiotic recombination  male meiotic nuclear division  female meiotic nuclear division  signal transduction  brain development  heart development  determination of adult lifespan  intrinsic apoptotic signaling pathway in response to DNA damage  post-embryonic development  response to ionizing radiation  regulation of autophagy  1-phosphatidylinositol-3-kinase activity  peptidyl-serine phosphorylation  negative regulation of B cell proliferation  cytoplasmic vesicle  regulation of telomere maintenance via telomerase  positive regulation of telomere maintenance via telomerase  protein complex binding  positive regulation of histone phosphorylation  V(D)J recombination  multicellular organism growth  phosphatidylinositol-3-phosphate biosynthetic process  peptidyl-serine autophosphorylation  lipoprotein catabolic process  regulation of apoptotic process  positive regulation of apoptotic process  positive regulation of DNA damage response, signal transduction by p53 class mediator  positive regulation of neuron apoptotic process  meiotic telomere clustering  protein autophosphorylation  protein autophosphorylation  protein dimerization activity  protein N-terminus binding  thymus development  oocyte development  neuron apoptotic process  regulation of telomerase activity  histone mRNA catabolic process  cellular response to gamma radiation  cellular response to X-ray  cellular response to nitrosative stress  signal transduction involved in mitotic G2 DNA damage checkpoint  replicative senescence  establishment of RNA localization to telomere  establishment of macromolecular complex localization to telomere  regulation of cellular response to heat  regulation of signal transduction by p53 class mediator  negative regulation of TORC1 signaling  negative regulation of telomere capping  positive regulation of telomere maintenance via telomere lengthening  positive regulation of telomerase catalytic core complex assembly  DNA repair complex  
    Pathways : BIOCARTA [Genes]   
    Pathways : KEGGNF-kappa B signaling pathway    FoxO signaling pathway    Cell cycle    p53 signaling pathway    Apoptosis    HTLV-I infection    Transcriptional misregulation in cancer    MicroRNAs in cancer   
    REACTOMEQ13315 [protein]
    REACTOME PathwaysR-HSA-912446 [pathway]   
    NDEx NetworkATM
    Atlas of Cancer Signalling NetworkATM
    Wikipedia pathwaysATM
    Orthology - Evolution
    OrthoDB472
    GeneTree (enSembl)ENSG00000149311
    Phylogenetic Trees/Animal Genes : TreeFamATM
    HOVERGENQ13315
    HOGENOMQ13315
    Homologs : HomoloGeneATM
    Homology/Alignments : Family Browser (UCSC)ATM
    Gene fusions - Rearrangements
    Fusion : MitelmanJARID2/ATM [6p22.3/11q22.3]  [t(6;11)(p22;q22)]  
    Fusion: TCGAJARID2 6p22.3 ATM 11q22.3 LUAD
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerATM [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)ATM
    dbVarATM
    ClinVarATM
    1000_GenomesATM 
    Exome Variant ServerATM
    ExAC (Exome Aggregation Consortium)ATM (select the gene name)
    Genetic variants : HAPMAP472
    Genomic Variants (DGV)ATM [DGVbeta]
    DECIPHERATM [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisATM 
    Mutations
    ICGC Data PortalATM 
    TCGA Data PortalATM 
    Broad Tumor PortalATM
    OASIS PortalATM [ Somatic mutations - Copy number]
    Cancer Gene: CensusATM 
    Somatic Mutations in Cancer : COSMICATM  [overview]  [genome browser]  [tissue]  [distribution]  
    Mutations and Diseases : HGMDATM
    intOGen PortalATM
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
    LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
    BioMutasearch ATM
    DgiDB (Drug Gene Interaction Database)ATM
    DoCM (Curated mutations)ATM (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)ATM (select a term)
    intoGenATM
    NCG5 (London)ATM
    Cancer3DATM(select the gene name)
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM114480    208900    607585   
    Orphanet104    22485    22484    10899    10693   
    MedgenATM
    Genetic Testing Registry ATM
    NextProtQ13315 [Medical]
    TSGene472
    GENETestsATM
    Target ValidationATM
    Huge Navigator ATM [HugePedia]
    snp3D : Map Gene to Disease472
    BioCentury BCIQATM
    ClinGenATM
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD472
    Chemical/Pharm GKB GenePA61
    Clinical trialATM
    Miscellaneous
    canSAR (ICR)ATM (select the gene name)
    Probes
    Litterature
    PubMed499 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineATM
    EVEXATM
    GoPubMedATM
    iHOPATM
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Fri Jun 30 11:01:13 CEST 2017
    Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us

    jlhuret@AtlasGeneticsOncology.org.