BLM (Bloom)

2005-05-01 Mounira Amor-Guéret Affiliation

Identity

HGNC

BLM

LOCATION

15q26.1

LOCUSID

641

ALIAS

BS,MGRISCE1,RECQ2,RECQL2,RECQL3

FUSION GENES

Show Gene Fusions

DNA/RNA

Transcription

4.4kb mRNA

Proteins

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

3-5DNA 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 name

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

Article Bibliography

Pubmed ID	Last Year	Title	Authors
11960380	2002	Bloom's syndrome protein response to ultraviolet-C radiation and hydroxyurea-mediated DNA synthesis inhibition.	Ababou M et al
10862105	2000	Identification of a novel BLM missense mutation (2706T>C) in a Moroccan patient with Bloom's syndrome.	Barakat A et al
15604258	2004	A major role for mitotic CDC2 kinase inactivation in the establishment of the mitotic DNA damage checkpoint.	Bayart E et al
11309417	2001	Regulation and localization of the Bloom syndrome protein in response to DNA damage.	Bischof O et al
11741924	2002	Dephosphorylation and subcellular compartment change of the mitotic Bloom's syndrome DNA helicase in response to ionizing radiation.	Dutertre S et al
8875252	1996	Molecular genetics of Bloom's syndrome.	Ellis NA et al
7585968	1995	The Bloom's syndrome gene product is homologous to RecQ helicases.	Ellis NA et al
9285778	1997	Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom's syndrome.	Foucault F et al
11781842	2001	The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control.	Garkavtsev IV et al
11971187	2002	Increased error-prone non homologous DNA end-joining--a proposed mechanism of chromosomal instability in Bloom's syndrome.	Gaymes TJ et al
10525530	1999	PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1.	Ishov AM et al
15143166	2004	Physical and functional interaction between the Bloom's syndrome gene product and the largest subunit of chromatin assembly factor 1.	Jiao R et al
15289897	2004	Relatively common mutations of the Bloom syndrome gene in the Japanese population.	Kaneko H et al
9388480	1997	BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal.	Kaneko H et al
9388193	1997	The Bloom's syndrome gene product is a 3'-5' DNA helicase.	Karow JK et al
10823897	2000	The Bloom's syndrome gene product promotes branch migration of holliday junctions.	Karow JK et al
9878247	1998	Cloning of two new human helicase genes of the RecQ family: biological significance of multiple species in higher eukaryotes.	Kitao S et al
12019152	2002	The BLM helicase is necessary for normal DNA double-strand break repair.	Langland G et al
10678659	2000	Rothmund-Thomson syndrome due to RECQ4 helicase mutations: report and clinical and molecular comparisons with Bloom syndrome and Werner syndrome.	Lindor NM et al
15845538	2005	RecQ family members combine strand pairing and unwinding activities to catalyze strand exchange.	Machwe A et al
12724401	2003	A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.	Meetei AR et al
11433031	2001	The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases.	Mohaghegh P et al
14576316	2003	Possible anti-recombinogenic role of Bloom's syndrome helicase in double-strand break processing.	Onclercq-Delic R et al
12181313	2002	Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases.	Opresko PL et al
11691925	2001	Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1.	Pedrazzi G et al
7961977	1994	Cloning and characterization of RECQL, a potential human homologue of the Escherichia coli DNA helicase RecQ.	Puranam KL et al
14577841	2003	Telomere and ribosomal DNA repeats are chromosomal targets of the bloom syndrome DNA helicase.	Schawalder J et al
7527136	1994	Molecular cloning of cDNA encoding human DNA helicase Q1 which has homology to Escherichia coli Rec Q helicase and localization of the gene at chromosome 12p12.	Seki M et al
15364958	2004	Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest.	Sengupta S et al
15509577	2004	Genetic interactions between BLM and DNA ligase IV in human cells.	So S et al
12444098	2002	The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis.	Stavropoulos DJ et al
9765292	1998	The Bloom's syndrome helicase unwinds G4 DNA.	Sun H et al
15579905	2005	Human Bloom protein stimulates flap endonuclease 1 activity by resolving DNA secondary structure.	Wang W et al
11399766	2001	Functional interaction of p53 and BLM DNA helicase in apoptosis.	Wang XW et al
10783165	2000	BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.	Wang Y et al
11278509	2001	Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51.	Wu L et al
12080066	2002	The processing of Holliday junctions by BLM and WRN helicases is regulated by p53.	Yang Q et al
10779560	2000	Nuclear structure in normal and Bloom syndrome cells.	Yankiwski V et al
8602509	1996	Positional cloning of the Werner's syndrome gene.	Yu CE et al
15805243	2005	BLM helicase facilitates Mus81 endonuclease activity in human cells.	Zhang R et al
11087418	2000	Binding and melting of D-loops by the Bloom syndrome helicase.	van Brabant AJ et al
11919194	2002	Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins.	von Kobbe C et al

Other Information

Locus ID:

NCBI: 641
MIM: 604610
HGNC: 1058
Ensembl: ENSG00000197299

Variants:

dbSNP: 641
ClinVar: 641
TCGA: ENSG00000197299
COSMIC: BLM

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000197299	ENST00000355112	P54132
ENSG00000197299	ENST00000559724	H0YLV8
ENSG00000197299	ENST00000560509	H0YNU5
ENSG00000197299	ENST00000648453	A0A3B3IT82

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Homologous recombination	KEGG	ko03440
Homologous recombination	KEGG	hsa03440
Fanconi anemia pathway	KEGG	ko03460
Fanconi anemia pathway	KEGG	hsa03460
BRCA1-associated genome surveillance complex (BASC)	KEGG	hsa_M00295
Bloom's syndrome complex	KEGG	hsa_M00414
BRCA1-associated genome surveillance complex (BASC)	KEGG	M00295
Bloom's syndrome complex	KEGG	M00414
Metabolism of proteins	REACTOME	R-HSA-392499
Post-translational protein modification	REACTOME	R-HSA-597592
SUMOylation	REACTOME	R-HSA-2990846
SUMO E3 ligases SUMOylate target proteins	REACTOME	R-HSA-3108232
SUMOylation of DNA damage response and repair proteins	REACTOME	R-HSA-3108214
Gene Expression	REACTOME	R-HSA-74160
Generic Transcription Pathway	REACTOME	R-HSA-212436
Transcriptional Regulation by TP53	REACTOME	R-HSA-3700989
Cell Cycle	REACTOME	R-HSA-1640170
Cell Cycle Checkpoints	REACTOME	R-HSA-69620
G2/M Checkpoints	REACTOME	R-HSA-69481
G2/M DNA damage checkpoint	REACTOME	R-HSA-69473
Meiosis	REACTOME	R-HSA-1500620
Meiotic recombination	REACTOME	R-HSA-912446
DNA Repair	REACTOME	R-HSA-73894
DNA Double-Strand Break Repair	REACTOME	R-HSA-5693532
Homology Directed Repair	REACTOME	R-HSA-5693538
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)	REACTOME	R-HSA-5693567
Processing of DNA double-strand break ends	REACTOME	R-HSA-5693607
HDR through Homologous Recombination (HRR)	REACTOME	R-HSA-5685942
Homologous DNA Pairing and Strand Exchange	REACTOME	R-HSA-5693579
Presynaptic phase of homologous DNA pairing and strand exchange	REACTOME	R-HSA-5693616
Resolution of D-Loop Structures	REACTOME	R-HSA-5693537
Resolution of D-loop Structures through Holliday Junction Intermediates	REACTOME	R-HSA-5693568
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	REACTOME	R-HSA-5693554
HDR through Single Strand Annealing (SSA)	REACTOME	R-HSA-5685938
Regulation of TP53 Activity	REACTOME	R-HSA-5633007
Regulation of TP53 Activity through Phosphorylation	REACTOME	R-HSA-6804756

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
38266639	2024	BLM and BRCA1-BARD1 coordinate complementary mechanisms of joint DNA molecule resolution.	1
38874681	2024	RecQ helicase expression in patients with telomeropathies.	0
38266639	2024	BLM and BRCA1-BARD1 coordinate complementary mechanisms of joint DNA molecule resolution.	1
38874681	2024	RecQ helicase expression in patients with telomeropathies.	0
37415147	2023	PARP1 negatively regulates transcription of BLM through its interaction with HSP90AB1 in prostate cancer.	0
37503837	2023	BLM helicase protein negatively regulates stress granule formation through unwinding RNA G-quadruplex structures.	0
37777511	2023	A CK2 and SUMO-dependent, PML NB-involved regulatory mechanism controlling BLM ubiquitination and G-quadruplex resolution.	3
37415147	2023	PARP1 negatively regulates transcription of BLM through its interaction with HSP90AB1 in prostate cancer.	0
37503837	2023	BLM helicase protein negatively regulates stress granule formation through unwinding RNA G-quadruplex structures.	0
37777511	2023	A CK2 and SUMO-dependent, PML NB-involved regulatory mechanism controlling BLM ubiquitination and G-quadruplex resolution.	3
35102151	2022	Duplex DNA and BLM regulate gate opening by the human TopoIIIα-RMI1-RMI2 complex.	6
35218564	2022	Phenotypic spectrum of BLM- and RMI1-related Bloom syndrome.	3
35922882	2022	Bloom Syndrome Helicase Compresses Single-Stranded DNA into Phase-Separated Condensates.	5
36004459	2022	Downregulation of BLM RecQ helicase inhibits proliferation, promotes the apoptosis and enhances the sensitivity of bladder cancer cells to cisplatin.	2
35102151	2022	Duplex DNA and BLM regulate gate opening by the human TopoIIIα-RMI1-RMI2 complex.	6

Citation

Mounira Amor-Guéret

BLM (Bloom)

Atlas Genet Cytogenet Oncol Haematol. 2005-05-01

Online version: http://atlasgeneticsoncology.org/gene/109

Historical Card

2000-09-01 BLM (Bloom) by Mounira Amor-Guéret Affiliation

1998-02-01 BLM (Bloom) by Jean-Loup Huret Affiliation

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France