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HUS1 (HUS1 checkpoint homolog (S. pombe))

Written2010-09Amrita Madabushi, Randall C Gunther, A-Lien Lu
Department of Biochemistry, Molecular Biology, School of Medicine, University of Maryland, 108 North Greene Street, Baltimore, Maryland 21201, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesHUS1 (S. pombe) checkpoint homolog
HUS1 checkpoint homolog (S. pombe)
Other alias
HGNC (Hugo) HUS1
LocusID (NCBI) 3364
Atlas_Id 40899
Location 7p12.3  [Link to chromosome band 7p12]
Location_base_pair Starts at 48002885 and ends at 48019222 bp from pter ( according to hg19-Feb_2009)  [Mapping HUS1.png]
Note NCBI accession: NM_004507.2; NP_004498.1.

DNA/RNA

 
  Figure 1. HUS1 gene adapted from NCBI database Homo sapiens chromosome 7, GrCh37 primary reference assembly with kilobases from the telomere of p-arm on bottom. The exons 1-8 are represented by boxes with transcribed and untranscribed sequences in pink and orange, respectively. The exon numbers are labeled on top. The grey arrowhead symbolizes the direction of transcription and the arrows show the ATG and the stop codons, respectively.
Description 15464 bp; 8 exons.
Transcription The transcribed mRNA has 2143 bp and the coding region is 840 bp, encodes a 280 amino acids, 31691 Da protein.
Pseudogene None.

Protein

 
  Figure 2. hHus1 and hRad1 associate with each other prior to forming the 9-1-1 complex with Rad9. In response to DNA damage and replication block, the 9-1-1 complex is loaded into DNA by Rad17/RFC clamp loader and acts as checkpoint sensor to activate ATM (ataxia telangiectasia [AT] mutated protein) or ATR (ATM- and Rad3-related protein) protein kinase. The 9-1-1 complex interacts with and stimulates many DNA repair enzymes involved in base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR). The damage recognition repair enzymes may serve as adaptors to signal DNA damage responses including enhanced DNA repair, cell cycle arrest, and apoptosis.
Description Amino acids: 280. Molecular weight: 31.7 kDa. Hus1 is a component of the 9-1-1 cell cycle checkpoint complex that plays a critical role in sensing DNA damage and maintaining genomic stability.
Expression Found in all tissues.
Localisation Nucleus and cytoplasm. In discrete nuclear foci upon DNA damage.
Function Hus1 along with and Rad1 forms the 9-1-1 complex (Hang and Lieberman, 2000; St Onge et al., 1999; Volkmer and Karnitz, 1999). Hus1 and Rad1 can also form a stable 1:1 complex (Doré et al., 2009; Sohn and Cho, 2009; Xu et al., 2009). The 9-1-complex is loaded onto the DNA by a specific clamp loader (Rad17-RFC2-RFC3-RFC4-RFC5) in response to many different genotoxic stresses (alkylation, oxidation, ultraviolet light radiation and ionizing radiation), and replication inhibitors (Bermudez et al., 2003; Ellison and Stillman, 2003). The Rad1-Rad9 interface may be opened to encircle DNA (Doré et al., 2009; Sohn and Cho, 2009; Xu et al., 2009).

The structure of the 9-1-1 complex (Doré et al., 2009; Sohn and Cho, 2009; Xu et al., 2009) is similar to the sliding clamp proliferating cell nuclear antigen protein (PCNA) (Gulbis et al., 1996; Krishna et al., 1994). Hus1 interacts with Rad9 and Rad1 through its N terminal domain and C terminal domain, respectively. The structure and surface charge distribution of the interdomain connecting loop (IDCL) of Hus1 differs from those of other two subunits (Doré et al., 2009; Sohn and Cho, 2009; Xu et al., 2009). The IDCL of Hus1 contains an N-terminal alpha helix and positive charge cluster. These differences among Hus1, Rad9, and Rad1 may contribute to different binding affinities to their partner proteins. For example, MutY homolog (MYH) has a strong preference to bind Hus1 (Chang and Lu, 2005; Shi et al., 2006).

Recent structural and functional analyses indicate that the Hus1 binding region of MYH adopts a stabilized conformation projecting away from the catalytic domain to form a docking scaffold for Hus1 and binds to Hus1 through electrostatic interaction (Luncsford et al., 2010).

The 9-1-1 complex is required to activate two checkpoint sensors-ATM (ataxia telangiectasia [AT] mutated protein) and ATR (ATM- and Rad3-related protein), which are phosphoinositol phosphate 3 kinase-related kinases (PIKKs) (Zhou and Elledge, 2000). The DNA-bound 9-1-1 complex facilitates ATM- or ATR-mediated phosphorylation of more than 700 proteins including Chk1, Chk2, p53, and BRCA1 (Zhou and Elledge, 2000). Hus1 facilitated phosphorylation of Chk1 kinase is required for the ATR-dependent checkpoint; and regulates S-phase progression, G2/M arrest, and replication fork stabilization (Sancar et al., 2004; Sancar et al., 2004). However, Hus1 is not required for Chk2 phosphorylation in response to certain genotoxins (Weiss et al., 2003).

Besides acting as a DNA damage sensor, the 9-1-1 complex plays an integral role in several DNA repair pathways including base excision repair (BER), mismatch repair (MMR), and nucleotide excision repair (NER) (see figure 2) (Helt et al., 2005).

In the BER pathway, the 9-1-1 complex facilitates and interacts with several DNA glycosylases including MYH (Chang and Lu, 2005; Shi et al., 2006; Chang and Lu, 2005; Shi et al., 2006), 8-oxoG glycosylase (OGG1) (Park et al., 2009), NEIL1 (Guan et al., 2007a), and thymine DNA glycosylase (TDG) (Guan et al., 2007b). The 9-1-1 complex also interacts with and stimulates other BER enzymes including APE1 (Gembka et al., 2007), POLbeta (Toueille et al., 2004), FEN1 (Friedrich-Heineken et al., 2005; Wang et al., 2004a), RPA (Wu et al., 2005), and DNA ligase 1 (Smirnova et al., 2005; Wang et al., 2006a). Thus, the 9-1-1 complex may provide a platform for the assembly and function of the BER machinery (Balakrishnan et al., 2009; Lu et al., 2006). The 9-1-1 complex enhances mismatch repair via direct interaction with mismatch recognition proteins (MSH2/MSH3, MSH2/MSH6, and MLH1/PMS2) (Bai et al., 2010; He et al., 2008). Hus1 interacts with MSH2/MSH3 and MSH2/MSH6, but not with MLH1/PMS2 (Bai et al., 2010; He et al., 2008).

In the NER pathway, interactions between Saccharomyces cerevisiae Rad14 (hXPA homolog) and the checkpoint proteins ScDdc1 (hRad9 homolog) and ScMec3 (hHus1 homolog) have been demonstrated (Giannattasio et al., 2004). Inactivation of NER by knock down of XPA and XPC resulted in a decrease of G1 phase cells that displayed Rad9 foci in response to UV light (Warmerdam et al., 2009). UV light-induced Rad9 foci also colocalized with TopBP1 and gamma-H2AX (Warmerdam et al., 2009).

Hus1 interacts with histone deacetylase HDAC1 (Cai et al., 2000). A novel pathway has been proposed that HDAC1 is involved in G(2)/M checkpoint control through the interaction with the 9-1-1 complex.

Jab1 physically associates with the 9-1-1 complex, causes the translocation of the 9-1-1 complex from the nucleus to the cytoplasm, and mediates the rapid degradation of the 9-1-1 complex (Huang et al., 2007).

Homology hHus1 homologues from many eukaryotes are highly conserved. The following diagram shows the sequence alignment of human Hus1 with Hus1 of fission yeast Schizosaccharomyces pombe. The N-terminal domain of Hus1 is structurally similar to the C-terminal domain. The structure of Hus1 (Doré et al., 2009; Sohn and Cho, 2009; Xu et al., 2009) is similar to those of Rad9, Rad1, and PCNA (Gulbis et al., 1996; Krishna et al., 1994).
 

Mutations

Note Complete inactivation of the mouse Hus1 results in chromosomal instability, genotoxin hypersensitivity, and embryonic lethality.

Implicated in

Note
  
Entity Breast cancer
Note Hus1 inactivation in the mammary epithelium resulted in genome damage that induced apoptosis and led to depletion of Hus1-null cells from the mammary gland. Dual inactivation of Hus1 and p53 in the mouse mammary gland results in accumulation of damaged cells and impaired tissue regeneration (Yazinski et al., 2009).
Oncogenesis Single nucleotide polymorphism (SNP) analysis supports the potential role of Hus1 in sporadic breast cancer (Vega et al., 2009). SNPs in hHUS1 at chromosome 7 base pair positions 47778020 (C) and 47789957 (G) are statistically associated with breast cancer development (Vega et al., 2009).
  
  
Entity Ovarian tumors
Oncogenesis Hus1 expression levels correlate significantly with the clinicopathologic factors of bad prognosis of ovarian tumors (de la Torre et al., 2008).
  
  
Entity Cancer therapy
Note The status of Hus1 can influence response to cancer therapy. Down-regulation of hHus1 by antisense RNA enhances the sensitivity of human lung carcinoma cells to cisplatin (a DNA cross-linker), presumably by enhancing apoptosis (Kinzel et al., 2002).
  
  
Entity Genomic stability
Note Inactivation of mouse or human Hus1 results in impaired DNA damage signaling and severe spontaneous chromosomal instability (Weiss et al., 2002; Weiss et al., 2000; Kinzel et al., 2002).
  
  
Entity Drug sensitivity
Note Cells lacking Hus1 are hypersensitive to certain genotoxins including camptothecin (CPT), hydroxyurea (HU), ultraviolet (UV), and ionizing radiation (IR) (Weiss et al., 2000; Wang et al., 2004b; Wang et al., 2006b). Loss of Hus1 sensitizes the cells to etoposide-induced apoptosis by inducing Bim and Puma expressions and releasing Rad9 into the cytosol (Levitt et al., 2005; Levitt et al., 2007; Meyerkord et al., 2008). The role of Hus1 affecting the sensitivity of cells to IR-induced killing is independent of nonhomologous end-joining (NHEJ) but might be linked to homologous recombination repair (HRR) (Wang et al., 2006b).
  
  
Entity Development
Note Targeted deletion of mouse Hus1 results in embryonic lethality (Weiss et al., 2000).
  
  
Entity Telomere maintenance
Note Severe telomere shortening has been observed in both Hus1-deficient mouse embryonic fibroblasts and thymocytes from conditional Hus1-knockout mice (Francia et al., 2006).
  
  
Entity HIV infection (AIDS)
Note Hus1 is required for Human Immunodeficiency Virus type 1 Vpr-mediated G2 cell cycle arrest (Zimmerman et al., 2004).
  

Bibliography

Interaction between human mismatch repair recognition proteins and checkpoint sensor Rad9-Rad1-Hus1.
Bai H, Madabushi A, Guan X, Lu AL.
DNA Repair (Amst). 2010 May 4;9(5):478-87. Epub 2010 Feb 25.
PMID 20188637
 
Long patch base excision repair proceeds via coordinated stimulation of the multienzyme DNA repair complex.
Balakrishnan L, Brandt PD, Lindsey-Boltz LA, Sancar A, Bambara RA.
J Biol Chem. 2009 May 29;284(22):15158-72. Epub 2009 Mar 27.
PMID 19329425
 
Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro.
Bermudez VP, Lindsey-Boltz LA, Cesare AJ, Maniwa Y, Griffith JD, Hurwitz J, Sancar A.
Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1633-8. Epub 2003 Feb 10.
PMID 12578958
 
HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two G2/M checkpoint Rad proteins.
Cai RL, Yan-Neale Y, Cueto MA, Xu H, Cohen D.
J Biol Chem. 2000 Sep 8;275(36):27909-16.
PMID 10846170
 
Interaction of checkpoint proteins Hus1/Rad1/Rad9 with DNA base excision repair enzyme MutY homolog in fission yeast, Schizosaccharomyces pombe.
Chang DY, Lu AL.
J Biol Chem. 2005 Jan 7;280(1):408-17. Epub 2004 Nov 8.
PMID 15533944
 
Crystal structure of the rad9-rad1-hus1 DNA damage checkpoint complex--implications for clamp loading and regulation.
Dore AS, Kilkenny ML, Rzechorzek NJ, Pearl LH.
Mol Cell. 2009 Jun 26;34(6):735-45. Epub 2009 May 14.
PMID 19446481
 
Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5' recessed DNA.
Ellison V, Stillman B.
PLoS Biol. 2003 Nov;1(2):E33. Epub 2003 Nov 17.
PMID 14624239
 
Telomere and telomerase modulation by the mammalian Rad9/Rad1/Hus1 DNA-damage-checkpoint complex.
Francia S, Weiss RS, Hande MP, Freire R, d'Adda di Fagagna F.
Curr Biol. 2006 Aug 8;16(15):1551-8.
PMID 16890531
 
The two DNA clamps Rad9/Rad1/Hus1 complex and proliferating cell nuclear antigen differentially regulate flap endonuclease 1 activity.
Friedrich-Heineken E, Toueille M, Tannler B, Burki C, Ferrari E, Hottiger MO, Hubscher U.
J Mol Biol. 2005 Nov 11;353(5):980-9. Epub 2005 Sep 27.
PMID 16216273
 
The checkpoint clamp, Rad9-Rad1-Hus1 complex, preferentially stimulates the activity of apurinic/apyrimidinic endonuclease 1 and DNA polymerase beta in long patch base excision repair.
Gembka A, Toueille M, Smirnova E, Poltz R, Ferrari E, Villani G, Hubscher U.
Nucleic Acids Res. 2007;35(8):2596-608. Epub 2007 Apr 10.
PMID 17426133
 
Physical and functional interactions between nucleotide excision repair and DNA damage checkpoint.
Giannattasio M, Lazzaro F, Longhese MP, Plevani P, Muzi-Falconi M.
EMBO J. 2004 Jan 28;23(2):429-38. Epub 2004 Jan 15.
PMID 14726955
 
The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase.
Guan X, Bai H, Shi G, Theriot CA, Hazra TK, Mitra S, Lu AL.
Nucleic Acids Res. 2007a;35(8):2463-72. Epub 2007 Mar 29.
PMID 17395641
 
The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates DNA repair enzyme TDG glycosylase.
Guan X, Madabushi A, Chang DY, Fitzgerald ME, Shi G, Drohat AC, Lu AL.
Nucleic Acids Res. 2007b;35(18):6207-18. Epub 2007 Sep 12.
PMID 17855402
 
Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA.
Gulbis JM, Kelman Z, Hurwitz J, O'Donnell M, Kuriyan J.
Cell. 1996 Oct 18;87(2):297-306.
PMID 8861913
 
Physical interactions among human checkpoint control proteins HUS1p, RAD1p, and RAD9p, and implications for the regulation of cell cycle progression.
Hang H, Lieberman HB.
Genomics. 2000 Apr 1;65(1):24-33.
PMID 10777662
 
Rad9 plays an important role in DNA mismatch repair through physical interaction with MLH1.
He W, Zhao Y, Zhang C, An L, Hu Z, Liu Y, Han L, Bi L, Xie Z, Xue P, Yang F, Hang H.
Nucleic Acids Res. 2008 Nov;36(20):6406-17. Epub 2008 Oct 8.
PMID 18842633
 
Evidence that DNA damage detection machinery participates in DNA repair.
Helt CE, Wang W, Keng PC, Bambara RA.
Cell Cycle. 2005 Apr;4(4):529-32. Epub 2005 Apr 10. (REVIEW)
PMID 15876866
 
Jab1 mediates protein degradation of the Rad9-Rad1-Hus1 checkpoint complex.
Huang J, Yuan H, Lu C, Liu X, Cao X, Wan M.
J Mol Biol. 2007 Aug 10;371(2):514-27. Epub 2007 Jun 4.
PMID 17583730
 
Downregulation of Hus1 by antisense oligonucleotides enhances the sensitivity of human lung carcinoma cells to cisplatin.
Kinzel B, Hall J, Natt F, Weiler J, Cohen D.
Cancer. 2002 Mar 15;94(6):1808-14.
PMID 11920544
 
Crystal structure of the eukaryotic DNA polymerase processivity factor PCNA.
Krishna TS, Kong XP, Gary S, Burgers PM, Kuriyan J.
Cell. 1994 Dec 30;79(7):1233-43.
PMID 8001157
 
Conditional inactivation of the mouse Hus1 cell cycle checkpoint gene.
Levitt PS, Liu H, Manning C, Weiss RS.
Genomics. 2005 Aug;86(2):212-24.
PMID 15919177
 
Genome maintenance defects in cultured cells and mice following partial inactivation of the essential cell cycle checkpoint gene Hus1.
Levitt PS, Zhu M, Cassano A, Yazinski SA, Liu H, Darfler J, Peters RM, Weiss RS.
Mol Cell Biol. 2007 Mar;27(6):2189-201. Epub 2007 Jan 12.
PMID 17220276
 
MutY and MutY homologs (MYH) in genome maintenance.
Lu AL, Bai H, Shi G, Chang DY.
Front Biosci. 2006 Sep 1;11:3062-80.
PMID 16720376
 
A structural hinge in eukaryotic MutY homologues mediates catalytic activity and Rad9-Rad1-Hus1 checkpoint complex interactions.
Luncsford PJ, Chang DY, Shi G, Bernstein J, Madabushi A, Patterson DN, Lu AL, Toth EA.
J Mol Biol. 2010 Oct 29;403(3):351-70. Epub 2010 Sep 15.
PMID 20816984
 
Loss of Hus1 sensitizes cells to etoposide-induced apoptosis by regulating BH3-only proteins.
Meyerkord CL, Takahashi Y, Araya R, Takada N, Weiss RS, Wang HG.
Oncogene. 2008 Dec 11;27(58):7248-59. Epub 2008 Sep 15.
PMID 18794804
 
Repair activities of human 8-oxoguanine DNA glycosylase are stimulated by the interaction with human checkpoint sensor Rad9-Rad1-Hus1 complex.
Park MJ, Park JH, Hahm SH, Ko SI, Lee YR, Chung JH, Sohn SY, Cho Y, Kang LW, Han YS.
DNA Repair (Amst). 2009 Oct 2;8(10):1190-200. Epub 2009 Jul 16.
PMID 19615952
 
Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints.
Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S.
Annu Rev Biochem. 2004;73:39-85. (REVIEW)
PMID 15189136
 
Physical and functional interactions between MutY glycosylase homologue (MYH) and checkpoint proteins Rad9-Rad1-Hus1.
Shi G, Chang DY, Cheng CC, Guan X, Venclovas C, Lu AL.
Biochem J. 2006 Nov 15;400(1):53-62.
PMID 16879101
 
The human checkpoint sensor and alternative DNA clamp Rad9-Rad1-Hus1 modulates the activity of DNA ligase I, a component of the long-patch base excision repair machinery.
Smirnova E, Toueille M, Markkanen E, Hubscher U.
Biochem J. 2005 Jul 1;389(Pt 1):13-7.
PMID 15871698
 
Crystal structure of the human rad9-hus1-rad1 clamp.
Sohn SY, Cho Y.
J Mol Biol. 2009 Jul 17;390(3):490-502. Epub 2009 May 21.
PMID 19464297
 
The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein that forms complexes with hRAD1 and hHUS1.
St Onge RP, Udell CM, Casselman R, Davey S.
Mol Biol Cell. 1999 Jun;10(6):1985-95.
PMID 10359610
 
The human Rad9/Rad1/Hus1 damage sensor clamp interacts with DNA polymerase beta and increases its DNA substrate utilisation efficiency: implications for DNA repair.
Toueille M, El-Andaloussi N, Frouin I, Freire R, Funk D, Shevelev I, Friedrich-Heineken E, Villani G, Hottiger MO, Hubscher U.
Nucleic Acids Res. 2004 Jun 22;32(11):3316-24. Print 2004.
PMID 15314187
 
Evaluating new candidate SNPs as low penetrance risk factors in sporadic breast cancer: a two-stage Spanish case-control study.
Vega A, Salas A, Milne RL, Carracedo B, Ribas G, Ruibal A, de Leon AC, Gonzalez-Hernandez A, Benitez J, Carracedo A.
Gynecol Oncol. 2009 Jan;112(1):210-4. Epub 2008 Oct 23.
PMID 18950845
 
Human homologs of Schizosaccharomyces pombe rad1, hus1, and rad9 form a DNA damage-responsive protein complex.
Volkmer E, Karnitz LM.
J Biol Chem. 1999 Jan 8;274(2):567-70.
PMID 9872989
 
The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1.
Wang W, Brandt P, Rossi ML, Lindsey-Boltz L, Podust V, Fanning E, Sancar A, Bambara RA.
Proc Natl Acad Sci U S A. 2004a Nov 30;101(48):16762-7. Epub 2004 Nov 19.
PMID 15556996
 
Mechanism of stimulation of human DNA ligase I by the Rad9-rad1-Hus1 checkpoint complex.
Wang W, Lindsey-Boltz LA, Sancar A, Bambara RA.
J Biol Chem. 2006b Jul 28;281(30):20865-72. Epub 2006 May 25.
PMID 16731526
 
Involvement of Hus1 in the chain elongation step of DNA replication after exposure to camptothecin or ionizing radiation.
Wang X, Guan J, Hu B, Weiss RS, Iliakis G, Wang Y.
Nucleic Acids Res. 2004b Feb 3;32(2):767-75. Print 2004.
PMID 14762204
 
The effect of Hus1 on ionizing radiation sensitivity is associated with homologous recombination repair but is independent of nonhomologous end-joining.
Wang X, Hu B, Weiss RS, Wang Y.
Oncogene. 2006a Mar 23;25(13):1980-3.
PMID 16278671
 
Cell cycle-dependent processing of DNA lesions controls localization of Rad9 to sites of genotoxic stress.
Warmerdam DO, Freire R, Kanaar R, Smits VA.
Cell Cycle. 2009 Jun 1;8(11):1765-74. Epub 2009 Jun 10.
PMID 19411845
 
Inactivation of mouse Hus1 results in genomic instability and impaired responses to genotoxic stress.
Weiss RS, Enoch T, Leder P.
Genes Dev. 2000 Aug 1;14(15):1886-98.
PMID 10921903
 
Critical role for mouse Hus1 in an S-phase DNA damage cell cycle checkpoint.
Weiss RS, Leder P, Vaziri C.
Mol Cell Biol. 2003 Feb;23(3):791-803.
PMID 12529385
 
Hus1 acts upstream of chk1 in a mammalian DNA damage response pathway.
Weiss RS, Matsuoka S, Elledge SJ, Leder P.
Curr Biol. 2002 Jan 8;12(1):73-7.
PMID 11790307
 
Interaction and colocalization of Rad9/Rad1/Hus1 checkpoint complex with replication protein A in human cells.
Wu X, Shell SM, Zou Y.
Oncogene. 2005 Jul 7;24(29):4728-35.
PMID 15897895
 
Structure and functional implications of the human rad9-hus1-rad1 cell cycle checkpoint complex.
Xu M, Bai L, Gong Y, Xie W, Hang H, Jiang T.
J Biol Chem. 2009 Jul 31;284(31):20457-61. Epub 2009 Jun 17.
PMID 19535328
 
Dual inactivation of Hus1 and p53 in the mouse mammary gland results in accumulation of damaged cells and impaired tissue regeneration.
Yazinski SA, Westcott PM, Ong K, Pinkas J, Peters RM, Weiss RS.
Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21282-7. Epub 2009 Nov 16.
PMID 19918068
 
The DNA damage response: putting checkpoints in perspective.
Zhou BB, Elledge SJ.
Nature. 2000 Nov 23;408(6811):433-9. (REVIEW)
PMID 11100718
 
Human immunodeficiency virus type 1 Vpr-mediated G2 arrest requires Rad17 and Hus1 and induces nuclear BRCA1 and gamma-H2AX focus formation.
Zimmerman ES, Chen J, Andersen JL, Ardon O, Dehart JL, Blackett J, Choudhary SK, Camerini D, Nghiem P, Planelles V.
Mol Cell Biol. 2004 Nov;24(21):9286-94.
PMID 15485898
 
Expression of DNA damage checkpoint protein Hus1 in epithelial ovarian tumors correlates with prognostic markers.
de la Torre J, Gil-Moreno A, Garcia A, Rojo F, Xercavins J, Salido E, Freire R.
Int J Gynecol Pathol. 2008 Jan;27(1):24-32.
PMID 18156970
 

Citation

This paper should be referenced as such :
Madabushi, A ; Gunther, RC ; Lu, AL. HUS1 (HUS1 checkpoint homolog (S
pombe))
Atlas Genet Cytogenet Oncol Haematol. 2011;15(5):455-459.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/HUS1ID40899ch7p12.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  i(7)(q10)


External links

Nomenclature
HGNC (Hugo)HUS1   5309
Cards
AtlasHUS1ID40899ch7p12
Entrez_Gene (NCBI)HUS1  3364  HUS1 checkpoint clamp component
AliaseshHUS1
GeneCards (Weizmann)HUS1
Ensembl hg19 (Hinxton)ENSG00000136273 [Gene_View]  chr7:48002885-48019222 [Contig_View]  HUS1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000136273 [Gene_View]  chr7:48002885-48019222 [Contig_View]  HUS1 [Vega]
ICGC DataPortalENSG00000136273
TCGA cBioPortalHUS1
AceView (NCBI)HUS1
Genatlas (Paris)HUS1
WikiGenes3364
SOURCE (Princeton)HUS1
Genetics Home Reference (NIH)HUS1
Genomic and cartography
GoldenPath hg19 (UCSC)HUS1  -     chr7:48002885-48019222 -  7p12.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)HUS1  -     7p12.3   [Description]    (hg38-Dec_2013)
EnsemblHUS1 - 7p12.3 [CytoView hg19]  HUS1 - 7p12.3 [CytoView hg38]
Mapping of homologs : NCBIHUS1 [Mapview hg19]  HUS1 [Mapview hg38]
OMIM603760   
Gene and transcription
Genbank (Entrez)AF076844 AF110393 AJ227901 AK290459 AK294117
RefSeq transcript (Entrez)NM_004507
RefSeq genomic (Entrez)NC_000007 NC_018918 NT_007819 NW_004929329
Consensus coding sequences : CCDS (NCBI)HUS1
Cluster EST : UnigeneHs.152983 [ NCBI ]
CGAP (NCI)Hs.152983
Alternative Splicing GalleryENSG00000136273
Gene ExpressionHUS1 [ NCBI-GEO ]   HUS1 [ EBI - ARRAY_EXPRESS ]   HUS1 [ SEEK ]   HUS1 [ MEM ]
Gene Expression Viewer (FireBrowse)HUS1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3364
GTEX Portal (Tissue expression)HUS1
Protein : pattern, domain, 3D structure
UniProt/SwissProtO60921   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO60921  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO60921
Splice isoforms : SwissVarO60921
PhosPhoSitePlusO60921
Domains : Interpro (EBI)Cell_cycle_HUS1    Hus1/Mec3   
Domain families : Pfam (Sanger)Hus1 (PF04005)   
Domain families : Pfam (NCBI)pfam04005   
Conserved Domain (NCBI)HUS1
DMDM Disease mutations3364
Blocks (Seattle)HUS1
PDB (SRS)3A1J    3G65    3GGR   
PDB (PDBSum)3A1J    3G65    3GGR   
PDB (IMB)3A1J    3G65    3GGR   
PDB (RSDB)3A1J    3G65    3GGR   
Structural Biology KnowledgeBase3A1J    3G65    3GGR   
SCOP (Structural Classification of Proteins)3A1J    3G65    3GGR   
CATH (Classification of proteins structures)3A1J    3G65    3GGR   
SuperfamilyO60921
Human Protein AtlasENSG00000136273
Peptide AtlasO60921
HPRD04787
IPIIPI00004712   IPI00924587   IPI00925054   IPI00925242   IPI00925779   IPI00926781   
Protein Interaction databases
DIP (DOE-UCLA)O60921
IntAct (EBI)O60921
FunCoupENSG00000136273
BioGRIDHUS1
STRING (EMBL)HUS1
ZODIACHUS1
Ontologies - Pathways
QuickGOO60921
Ontology : AmiGODNA damage checkpoint  double-strand break repair via homologous recombination  regulation of protein phosphorylation  protein binding  nucleus  nucleoplasm  nucleolus  cytosol  DNA replication  DNA repair  nucleotide-excision repair  protein phosphorylation  cellular response to DNA damage stimulus  negative regulation of DNA replication  response to UV  embryo development  checkpoint clamp complex  intra-S DNA damage checkpoint  mitotic DNA replication checkpoint  site of double-strand break  meiotic DNA integrity checkpoint  cellular response to ionizing radiation  regulation of signal transduction by p53 class mediator  
Ontology : EGO-EBIDNA damage checkpoint  double-strand break repair via homologous recombination  regulation of protein phosphorylation  protein binding  nucleus  nucleoplasm  nucleolus  cytosol  DNA replication  DNA repair  nucleotide-excision repair  protein phosphorylation  cellular response to DNA damage stimulus  negative regulation of DNA replication  response to UV  embryo development  checkpoint clamp complex  intra-S DNA damage checkpoint  mitotic DNA replication checkpoint  site of double-strand break  meiotic DNA integrity checkpoint  cellular response to ionizing radiation  regulation of signal transduction by p53 class mediator  
Pathways : BIOCARTARole of BRCA1, BRCA2 and ATR in Cancer Susceptibility [Genes]   
REACTOMEO60921 [protein]
REACTOME Pathways176187 [pathway]   5685938 [pathway]   5693607 [pathway]   5693616 [pathway]   6804756 [pathway]   69473 [pathway]   
NDEx NetworkHUS1
Atlas of Cancer Signalling NetworkHUS1
Wikipedia pathwaysHUS1
Orthology - Evolution
OrthoDB3364
GeneTree (enSembl)ENSG00000136273
Phylogenetic Trees/Animal Genes : TreeFamHUS1
HOVERGENO60921
HOGENOMO60921
Homologs : HomoloGeneHUS1
Homology/Alignments : Family Browser (UCSC)HUS1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerHUS1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)HUS1
dbVarHUS1
ClinVarHUS1
1000_GenomesHUS1 
Exome Variant ServerHUS1
ExAC (Exome Aggregation Consortium)HUS1 (select the gene name)
Genetic variants : HAPMAP3364
Genomic Variants (DGV)HUS1 [DGVbeta]
DECIPHER (Syndromes)7:48002885-48019222  ENSG00000136273
CONAN: Copy Number AnalysisHUS1 
Mutations
ICGC Data PortalHUS1 
TCGA Data PortalHUS1 
Broad Tumor PortalHUS1
OASIS PortalHUS1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICHUS1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDHUS1
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
BioMutasearch HUS1
DgiDB (Drug Gene Interaction Database)HUS1
DoCM (Curated mutations)HUS1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)HUS1 (select a term)
intoGenHUS1
NCG5 (London)HUS1
Cancer3DHUS1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603760   
Orphanet
MedgenHUS1
Genetic Testing Registry HUS1
NextProtO60921 [Medical]
TSGene3364
GENETestsHUS1
Huge Navigator HUS1 [HugePedia]
snp3D : Map Gene to Disease3364
BioCentury BCIQHUS1
ClinGenHUS1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3364
Chemical/Pharm GKB GenePA29564
Clinical trialHUS1
Miscellaneous
canSAR (ICR)HUS1 (select the gene name)
Probes
Litterature
PubMed66 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineHUS1
EVEXHUS1
GoPubMedHUS1
iHOPHUS1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:33:17 CEST 2017

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