BLM (Bloom)

Identity

Hugo	BLM
Location	15q26.1

DNA/RNA

Transcription

4.4kb mRNA

Protein

Description	1417 amino acids; ATP binding in amino acid 689-696; DEAH box in 795-798; two putative nuclear localization signals in the C-term in 1334-1349
Expression	accumulates to high levels in S phase of the cell cycle, persists in G2/M and sharply declines in G1. Hyperphoshorylated in mitosis
Localisation	nuclear (PML nuclear bodies and nucleolus)
Function	3'-5'DNA helicase; probable role in DNA replication and double-strand break repair Preferred substrates : G-quadruplex DNA, D-loops structures and X-junctions. Recombinant protein promotes ATP-dependent branch migration of Hollyday junctions, effects, with topoisomerase III?, the resolution of a recombination intermediate containing a double Holliday junction with no flanking sequence exchanges, and possess a strand pairing activity. Recombinant BLM possess a strand pairing activity. Participates in a supercomplex of BRCA1 -associated proteins named BASC (BRCA1-Associated genome Surveillance Complex) containing ATM (defective in ataxia telangiectasia), NBS1 (defective in Nijmegen syndrome) and MRE11 (defective in ataxia-telangiectasia-like disorder), MLH1, MSH2 and MSH6, which are involved in human non-polyposis colorectal cancer, RAD50 and DNA replication factor C. Participates in a complex named BRAFT (BLM, RPA, FA, Topoisomerase III) containing five of the Fanconia Anemia (FA) complementation group proteins (FANCA, FANCG, FANCC, FANCE and FANCF). Interacts physically and/or functionally with p53, 53BP1, WRN, MLH1, RAD51, TRF2, ATR, the largest subunit of CAF-1, ligase IV, FEN1, Mus81, the monoubiquitinated FANCD2 isoform Is Associated with telomeres and ribosomal DNA repeats. Is phosphorylated in mitotic cells through the cdc2 pathway, and in response to DNA damaging agents or stalled replication forks.
Homology	homologous to RecQ helicases, a subfamily of DExH box-containing helicases; in particular, similarity with the four known human members in the RecQ subfamily, human RecQL, human Wrn, the product of the Werner syndrome gene, and the human RecQL4, involved in the Rothmund-Thomson syndrome, and RecQL5 proteins

Mutations

Germinal

five BLM mutations introducing amino acid substitutions and four BLM mutations introducing premature nonsense codons into the coding sequence have been described to date; one BLM mutation consisting in a 6 bp deletion accompanied by a 7 bp insertion at nucleic acid position 2281 is common in patients from Ashkenazi Jewish ancestry, leading to a truncated protein of 739 amino acids in length; two BLM mutations, 631delCAA and 1610insA were detected in japanese patients.

Implicated in

Entity	Bloom syndrome
Disease	Bloom syndrome is a chromosome instability syndrome/cancer prone disease (at risk of numerous, early occurring cancers of various types)
Prognosis	1/3 of patients are dead at mean age 24 yrs, and the mean age of the 2/3 remaining alive patients is 22 yrs
Cytogenetics	chromatid/chromosome breaks; triradial and quadriradial figures, highly elevated spontaneous sister chromatid exchange rate

External links

	Nomenclature
Hugo	BLM
GDB	BLM
Entrez_Gene	BLM  641  Bloom syndrome
	Cards
Atlas	BLM109
GeneCards	BLM
Ensembl	BLM [Search_View]   ENSG00000197299 [Gene_View]
Genatlas	BLM
GeneLynx	BLM
eGenome	BLM
euGene	641
	Genomic and cartography
GoldenPath	BLM  -  15q26.1   chr15:89061583-89159688 +  15q26.1   [Description]    (hg18-Mar_2006)
Ensembl	BLM - 15q26.1 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	BLM
	Gene and transcription
Genbank	AK314262 [ ENTREZ ]
Genbank	BC034480 [ ENTREZ ]
Genbank	BC062697 [ ENTREZ ]
Genbank	BC093622 [ ENTREZ ]
Genbank	BC101567 [ ENTREZ ]
RefSeq	NM_000057 [ SRS ]    NM_000057 [ ENTREZ ]
RefSeq	AC_000058 [ SRS ]    AC_000058 [ ENTREZ ]
RefSeq	AC_000147 [ SRS ]    AC_000147 [ ENTREZ ]
RefSeq	NC_000015 [ SRS ]    NC_000015 [ ENTREZ ]
RefSeq	NG_007272 [ SRS ]    NG_007272 [ ENTREZ ]
RefSeq	NT_010274 [ SRS ]    NT_010274 [ ENTREZ ]
RefSeq	NW_001838222 [ SRS ]    NW_001838222 [ ENTREZ ]
RefSeq	NW_925940 [ SRS ]    NW_925940 [ ENTREZ ]
AceView	BLM AceView - NCBI
Unigene	Hs.169348 [ SRS ]    Hs.169348 [ NCBI ]     HS169348 [ spliceNest ]
Fast-db	10467 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P54132 [ SRS]    P54132 [ EXPASY ]     P54132 [ INTERPRO ]
Prosite	PS00690 DEAH_ATP_HELICASE [ SRS ]    PS00690 DEAH_ATP_HELICASE [ Expasy ]
Prosite	PS51192 HELICASE_ATP_BIND_1 [ SRS ]    PS51192 HELICASE_ATP_BIND_1 [ Expasy ]
Prosite	PS51194 HELICASE_CTER [ SRS ]    PS51194 HELICASE_CTER [ Expasy ]
Prosite	PS50967 HRDC [ SRS ]    PS50967 HRDC [ Expasy ]
Interpro	IPR012532 BDHCT [ SRS ]    IPR012532 BDHCT [ EBI ]
Interpro	IPR014001 DEAD-like_N [ SRS ]    IPR014001 DEAD-like_N [ EBI ]
Interpro	IPR001650 DNA/RNA_helicase_C [ SRS ]    IPR001650 DNA/RNA_helicase_C [ EBI ]
Interpro	IPR011545 DNA/RNA_helicase_DEAD/DEAH_N [ SRS ]    IPR011545 DNA/RNA_helicase_DEAD/DEAH_N [ EBI ]
Interpro	IPR002464 DNA/RNA_helicase_DEAH_CS [ SRS ]    IPR002464 DNA/RNA_helicase_DEAH_CS [ EBI ]
Interpro	IPR004589 DNA_helicase_ATP-dep_RecQ [ SRS ]    IPR004589 DNA_helicase_ATP-dep_RecQ [ EBI ]
Interpro	IPR014021 Helicase_SF1/SF2_ATP-bd [ SRS ]    IPR014021 Helicase_SF1/SF2_ATP-bd [ EBI ]
Interpro	IPR002121 HRDC [ SRS ]    IPR002121 HRDC [ EBI ]
CluSTr	P54132
Pfam	PF08072 BDHCT [ SRS ]    PF08072 BDHCT [ Sanger ]    pfam08072 [ NCBI-CDD ]
Pfam	PF00270 DEAD [ SRS ]    PF00270 DEAD [ Sanger ]    pfam00270 [ NCBI-CDD ]
Pfam	PF00271 Helicase_C [ SRS ]    PF00271 Helicase_C [ Sanger ]    pfam00271 [ NCBI-CDD ]
Pfam	PF00570 HRDC [ SRS ]    PF00570 HRDC [ Sanger ]    pfam00570 [ NCBI-CDD ]
Smart	SM00487 DEXDc [EMBL]
Smart	SM00490 HELICc [EMBL]
Smart	SM00341 HRDC [EMBL]
Blocks	P54132
PDB	BLM [ SRS ]    BLM [ PdbSum ],   BLM [ IMB ]   BLM [ RSDB ]
HPRD	05211
	Protein Interaction databases
DIP	P54132
IntAct	P54132
	Polymorphism : SNP, mutations, diseases
OMIM	210900;604610    [ map ]
GENECLINICS	210900;604610
SNP	BLM [dbSNP-NCBI]
SNP	NM_000057 [SNP-NCI]
SNP	BLM [GeneSNPs - Utah]  BLM] [HGBASE - SRS]
HAPMAP	BLM [HAPMAP]
COSMIC	BLM [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	BLM
	General knowledge
Family Browser	BLM [UCSC Family Browser]
SOURCE	NM_000057
SMD	Hs.169348
SAGE	Hs.169348
Enzyme	3.6.1.- [ Enzyme-Expasy ]   3.6.1.- [ Enzyme-SRS ]   3.6.1.- [ IntEnz-EBI ]   3.6.1.- [ BRENDA ]   3.6.1.- [ KEGG ]   3.6.1.- [ WIT ]
GO	regulation of cyclin-dependent protein kinase activity [Amigo]  regulation of cyclin-dependent protein kinase activity
GO	G2 phase of mitotic cell cycle [Amigo]  G2 phase of mitotic cell cycle
GO	nucleotide binding [Amigo]  nucleotide binding
GO	bubble DNA binding [Amigo]  bubble DNA binding
GO	telomere maintenance [Amigo]  telomere maintenance
GO	double-strand break repair via homologous recombination [Amigo]  double-strand break repair via homologous recombination
GO	DNA strand annealing activity [Amigo]  DNA strand annealing activity
GO	chromosome, telomeric region [Amigo]  chromosome, telomeric region
GO	lateral element [Amigo]  lateral element
GO	p53 binding [Amigo]  p53 binding
GO	DNA binding [Amigo]  DNA binding
GO	ATP binding [Amigo]  ATP binding
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	replication fork [Amigo]  replication fork
GO	nucleolus [Amigo]  nucleolus
GO	DNA replication [Amigo]  DNA replication
GO	DNA repair [Amigo]  DNA repair
GO	four-way junction helicase activity [Amigo]  four-way junction helicase activity
GO	response to X-ray [Amigo]  response to X-ray
GO	nuclear matrix [Amigo]  nuclear matrix
GO	PML body [Amigo]  PML body
GO	PML body [Amigo]  PML body
GO	hydrolase activity [Amigo]  hydrolase activity
GO	hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides [Amigo]  hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
GO	ATPase activity [Amigo]  ATPase activity
GO	replication fork processing [Amigo]  replication fork processing
GO	G2/M transition DNA damage checkpoint [Amigo]  G2/M transition DNA damage checkpoint
GO	ATP-dependent 3'-5' DNA helicase activity [Amigo]  ATP-dependent 3'-5' DNA helicase activity
GO	cellular metabolic process [Amigo]  cellular metabolic process
GO	positive regulation of transcription [Amigo]  positive regulation of transcription
GO	negative regulation of mitotic recombination [Amigo]  negative regulation of mitotic recombination
GO	alpha-beta T cell differentiation [Amigo]  alpha-beta T cell differentiation
GO	positive regulation of alpha-beta T cell proliferation [Amigo]  positive regulation of alpha-beta T cell proliferation
GO	replication fork protection [Amigo]  replication fork protection
GO	regulation of binding [Amigo]  regulation of binding
GO	protein oligomerization [Amigo]  protein oligomerization
GO	chromosome organization and biogenesis [Amigo]  chromosome organization and biogenesis
GO	negative regulation of cell division [Amigo]  negative regulation of cell division
GO	G-quadruplex DNA binding [Amigo]  G-quadruplex DNA binding
PubGene	BLM
TreeFam	BLM
CTD	641 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	BLM Related clones (RZPD - Berlin)
	PubMed
PubMed	109 Pubmed reference(s) in LocusLink

Bibliography

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PMID 8875252

Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom's syndrome.

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BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal.

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PMID 9878247

The Bloom's syndrome helicase unwinds G4 DNA.

Sun H, Karow JK, Hickson ID, Maizels N

The Journal of biological chemistry. 1998 ; 273 (42) : 27587-27592.

PMID 9765292

PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1.

Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T, Yeh ET, Strauss JF 3rd, Maul GG

The Journal of cell biology. 1999 ; 147 (2) : 221-234.

PMID 10525530

Nuclear structure in normal and Bloom syndrome cells.

Yankiwski V, Marciniak RA, Guarente L, Neff NF

Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (10) : 5214-5219.

PMID 10779560

Rothmund-Thomson syndrome due to RECQ4 helicase mutations: report and clinical and molecular comparisons with Bloom syndrome and Werner syndrome.

Lindor NM, Furuichi Y, Kitao S, Shimamoto A, Arndt C, Jalal S

American journal of medical genetics. 2000 ; 90 (3) : 223-228.

PMID 10678659

Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase.

Dutertre S, Ababou M, Onclercq R, Delic J, Chatton B, Jaulin C, Amor-Guˆ©ret M

Oncogene. 2000 ; 19 (23) : 2731-2738.

PMID 10851073

Identification of a novel BLM missense mutation (2706T>C) in a Moroccan patient with Bloom's syndrome.

Barakat A, Ababou M, Onclercq R, Dutertre S, Chadli E, Hda N, Benslimane A, Amor-Guˆ©ret M

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PMID 10862105

Binding and melting of D-loops by the Bloom syndrome helicase.

van Brabant AJ, Ye T, Sanz M, German III JL, Ellis NA, Holloman WK

Biochemistry. 2000 ; 39 (47) : 14617-14625.

PMID 11087418

ATM-dependent phosphorylation and accumulation of endogenous BLM protein in response to ionizing radiation.

Ababou M, Dutertre S, Lˆ©cluse Y, Onclercq R, Chatton B, Amor-Guˆ©ret M

Oncogene. 2000 ; 19 (52) : 5955-5963.

PMID 11146546

The Bloom's syndrome gene product promotes branch migration of holliday junctions.

Karow JK, Constantinou A, Li JL, West SC, Hickson ID

Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (12) : 6504-6508.

PMID 10823897

BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.

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Genes & development. 2000 ; 14 (8) : 927-939.

PMID 10783165

The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases.

Mohaghegh P, Karow JK, Brosh Jr RM Jr, Bohr VA, Hickson ID

Nucleic acids research. 2001 ; 29 (13) : 2843-2849.

PMID 11433031

The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair.

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Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1.

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PMID 11691925

The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control.

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PMID 11781842

Functional interaction of p53 and BLM DNA helicase in apoptosis.

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PMID 11399766

Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51.

Wu L, Davies SL, Levitt NC, Hickson ID

The Journal of biological chemistry. 2001 ; 276 (22) : 19375-19381.

PMID 11278509

Regulation and localization of the Bloom syndrome protein in response to DNA damage.

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The Journal of cell biology. 2001 ; 153 (2) : 367-380.

PMID 11309417

The processing of Holliday junctions by BLM and WRN helicases is regulated by p53.

Yang Q, Zhang R, Wang XW, Spillare EA, Linke SP, Subramanian D, Griffith JD, Li JL, Hickson ID, Shen JC, Loeb LA, Mazur SJ, Appella E, Brosh RM Jr, Karmakar P, Bohr VA, Harris CC

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PMID 12080066

Bloom's syndrome protein response to ultraviolet-C radiation and hydroxyurea-mediated DNA synthesis inhibition.

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The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis.

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Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases.

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PMID 12181313

The BLM helicase is necessary for normal DNA double-strand break repair.

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PMID 12019152

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PMID 11971187

Dephosphorylation and subcellular compartment change of the mitotic Bloom's syndrome DNA helicase in response to ionizing radiation.

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PMID 11741924

A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.

Meetei AR, Sechi S, Wallisch M, Yang D, Young MK, Joenje H, Hoatlin ME, Wang W

Molecular and cellular biology. 2003 ; 23 (10) : 3417-3426.

PMID 12724401

BLM helicase-dependent transport of p53 to sites of stalled DNA replication forks modulates homologous recombination.

Sengupta S, Linke SP, Pedeux R, Yang Q, Farnsworth J, Garfield SH, Valerie K, Shay JW, Ellis NA, Wasylyk B, Harris CC

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PMID 12606585

Possible anti-recombinogenic role of Bloom's syndrome helicase in double-strand break processing.

Onclercq-Delic R, Calsou P, Delteil C, Salles B, Papadopoulo D, Amor-Guˆ©ret M

Nucleic acids research. 2003 ; 31 (21) : 6272-6282.

PMID 14576316

Telomere and ribosomal DNA repeats are chromosomal targets of the bloom syndrome DNA helicase.

Schawalder J, Paric E, Neff NF

BMC cell biology. 2003 ; 4 : page 15.

PMID 14577841

Relatively common mutations of the Bloom syndrome gene in the Japanese population.

Kaneko H, Isogai K, Fukao T, Matsui E, Kasahara K, Yachie A, Seki H, Koizumi S, Arai M, Utunomiya J, Miki Y, Kondo N

International journal of molecular medicine. 2004 ; 14 (3) : 439-442.

PMID 15289897

Physical and functional interaction between the Bloom's syndrome gene product and the largest subunit of chromatin assembly factor 1.

Jiao R, Bachrati CZ, Pedrazzi G, Kuster P, Petkovic M, Li JL, Egli D, Hickson ID, Stagljar I

Molecular and cellular biology. 2004 ; 24 (11) : 4710-4719.

PMID 15143166

Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest.

Sengupta S, Robles AI, Linke SP, Sinogeeva NI, Zhang R, Pedeux R, Ward IM, Celeste A, Nussenzweig A, Chen J, Halazonetis TD, Harris CC

The Journal of cell biology. 2004 ; 166 (6) : 801-813.

PMID 15364958

Human Bloom protein stimulates flap endonuclease 1 activity by resolving DNA secondary structure.

Wang W, Bambara RA

The Journal of biological chemistry. 2005 ; 280 (7) : 5391-5399.

PMID 15579905

Genetic interactions between BLM and DNA ligase IV in human cells.

So S, Adachi N, Lieber MR, Koyama H

The Journal of biological chemistry. 2004 ; 279 (53) : 55433-55442.

PMID 15509577

A major role for mitotic CDC2 kinase inactivation in the establishment of the mitotic DNA damage checkpoint.

Bayart E, Grigorieva O, Leibovitch S, Onclercq-Delic R, Amor-Guˆ©ret M

Cancer research. 2004 ; 64 (24) : 8954-8959.

PMID 15604258

BLM helicase facilitates Mus81 endonuclease activity in human cells.

Zhang R, Sengupta S, Yang Q, Linke SP, Yanaihara N, Bradsher J, Blais V, McGowan CH, Harris CC

Cancer research. 2005 ; 65 (7) : 2526-2531.

PMID 15805243

RecQ family members combine strand pairing and unwinding activities to catalyze strand exchange.

Machwe A, Xiao L, Groden J, Matson SW, Orren DK

The Journal of biological chemistry. 2005 ; 280 (24) : 23397-23407.

PMID 15845538

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Contributor(s)

Written	02-1998	Jean-Loup Huret
Updated	09-2000	Mounira Amor-Guéret
Updated	05-2005	Mounira Amor-Guéret

Citation

This paper should be referenced as such :

Huret JL . BLM (Bloom). Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://AtlasGeneticsOncology.org/Genes/BLM109.html

Amor-Guéret M . BLM (Bloom). Atlas Genet Cytogenet Oncol Haematol. September 2000 . URL : http://AtlasGeneticsOncology.org/Genes/BLM109.html

Amor-Guéret M . BLM (Bloom). Atlas Genet Cytogenet Oncol Haematol. May 2005 . URL : http://AtlasGeneticsOncology.org/Genes/BLM109.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Jul 14 17:42:19 2008