BLM
The Bloom syndrome gene product is related to the RecQ subset of DExH box-containing DNA helicases and has both DNA-stimulated ATPase and ATP-dependent DNA helicase activities. Mutations causing Bloom syndrome delete or alter helicase motifs and may disable the 3'-5' helicase activity. The normal protein may act to suppress inappropriate recombination. [provided by RefSeq, Jul 2008]
Full Name
Bloom Syndrome RecQ Like Helicase
Function
ATP-dependent DNA helicase that unwinds single- and double-stranded DNA in a 3'-5' direction (PubMed:9388193, PubMed:24816114, PubMed:25901030).
Participates in DNA replication and repair (PubMed:12019152, PubMed:21325134, PubMed:23509288).
Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA (PubMed:21325134).
Negatively regulates sister chromatid exchange (SCE) (PubMed:25901030).
Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution (PubMed:25901030).
Binds single-stranded DNA (ssDNA), forked duplex DNA and DNA Holliday junction (PubMed:20639533, PubMed:24257077, PubMed:25901030).
Recruited by the KHDC3L-OOEP scaffold to DNA replication forks where it is retained by TRIM25 ubiquitination, it thereby promotes the restart of stalled replication forks (By similarity).
Biological Process
Cellular response to camptothecin Source: UniProtKB
Cellular response to DNA damage stimulus Source: UniProtKB
Cellular response to hydroxyurea Source: UniProtKB
Cellular response to ionizing radiation Source: UniProtKB
DNA double-strand break processing Source: UniProtKB
DNA duplex unwinding Source: UniProtKB
DNA recombination Source: GO_Central
DNA repair Source: GO_Central
DNA replication Source: BHF-UCL
DNA unwinding involved in DNA replication Source: GO_Central
Double-strand break repair via homologous recombination Source: GO_Central
G-quadruplex DNA unwinding Source: BHF-UCL
Mitotic G2 DNA damage checkpoint Source: UniProtKB
Negative regulation of cell division Source: UniProtKB
Negative regulation of DNA recombination Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: UniProtKB
Protein complex oligomerization Source: UniProtKB
Protein homooligomerization Source: UniProtKB
Regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
Regulation of DNA-dependent DNA replication Source: UniProtKB
Regulation of signal transduction by p53 class mediator Source: Reactome
Replication fork processing Source: UniProtKB
Replication fork protection Source: UniProtKB
Response to X-ray Source: UniProtKB
T-circle formation Source: BHF-UCL
Telomere maintenance Source: GO_Central
Telomere maintenance via semi-conservative replication Source: Reactome
Telomeric D-loop disassembly Source: BHF-UCL
Cellular Location
Nucleus. Together with SPIDR, is redistributed in discrete nuclear DNA damage-induced foci following hydroxyurea (HU) or camptothecin (CPT) treatment. Accumulated at sites of DNA damage in a RMI complex- and SPIDR-dependent manner.
Involvement in disease
Bloom syndrome (BLM): An autosomal recessive disorder. It is characterized by proportionate pre- and postnatal growth deficiency, sun-sensitive telangiectatic hypo- and hyperpigmented skin, predisposition to malignancy, and chromosomal instability.
PTM
Poly-ubiquitinated by TRIM25 at Lys-259.
Phosphorylated in response to DNA damage. Phosphorylation requires the FANCA-FANCC-FANCE-FANCF-FANCG protein complex, as well as the presence of RMI1.