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WRN

Domain

The KBM 2 (Ku-binding motif 2) and XLM (XLF-like motif) mediate cooperative interaction with XRCC5/Ku80 and XRCC6/Ku70 and recruitment to DNA damage sites (PubMed:27063109). The isolated helicase core (residues 517-1093) interacts weakly with the HDRC domain in vitro (PubMed:33199508).

Function

Multifunctional enzyme that has magnesium and ATP-dependent 3'-5' DNA-helicase activity on partially duplex substrates (PubMed:9224595, PubMed:9288107, PubMed:9611231). Also has 3'->5' exonuclease activity towards double-stranded (ds)DNA with a 5'-overhang (PubMed:11863428). Has no nuclease activity towards single-stranded (ss)DNA or blunt-ended dsDNA (PubMed:11863428). Helicase activity is most efficient with (d)ATP, but (d)CTP will substitute with reduced efficiency; strand displacement is enhanced by single-strand binding-protein (heterotrimeric replication protein A complex, RPA1, RPA2, RPA3) (PubMed:9611231). Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity). Plays a role in double-strand break repair after gamma-irradiation (PubMed:9224595, PubMed:9288107, PubMed:9611231). Unwinds some G-quadruplex DNA (d(CGG)n tracts); unwinding seems to occur in both 5'-3' and 3'-5' direction and requires a short single-stranded tail (PubMed:10212265). d(CGG)n tracts have a propensity to assemble into tetraplex structures; other G-rich substrates from a telomeric or IgG switch sequence are not unwound (PubMed:10212265). Depletion leads to chromosomal breaks and genome instability (PubMed:33199508).

Involvement in disease

Werner syndrome

WRN

A rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus, ocular cataracts and osteoporosis. The major cause of death, at a median age of 47, is myocardial infarction.

None

The disease is caused by variants affecting the gene represented in this entry.

Colorectal cancer

CRC

A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.

None

The disease may be caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylated by PRKDC.

Sequence Similarities

Belongs to the helicase family. RecQ subfamily.

Cellular localization

Alternative names

RECQ3, RECQL2, WRN, Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN, RecQ protein-like 2, Werner syndrome protein

swissprot:Q14191 entrezGene:7486 omim:604611

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