Werner syndrome ATP-dependent helicase (WRN, RECQ3, RECQL2)
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Function
- helicase essential for the formation of DNA replication focal centers;
- stably associates with foci elements generating binding sites for RPA
- has both Mg+2 & ATP-dependent DNA-helicase activity & 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang
- has no nuclease activity towards single-stranded DNA or blunt-ended double-stranded DNA
- binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks & 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
- may be involved in the control of genomic stability
- role in formation of DNA replication focal centers
- stably associates with foci elements generating binding sites for RP-A (putative)
- role in double-strand break repair after gamma-irradiation
- phosphorylated by PRKDC
- interacts via its N-terminal domain with WRNIP1
- interacts with EXO1, PCNA & SUPV3L1
- monomer, & homooligomer
- may exist as homodimer, homotrimer, homotetramer &/or homohexamer
- homotetramer, or homohexamer, when bound to DNA
formerly
- phosphorylated upon DNA damage, probably by ATM or ATR
Structure
- belongs to the helicase family, recQ subfamily
- contains 1 3'-5' exonuclease domain
- contains 1 helicase ATP-binding domain
- contains 1 helicase C-terminal domain
- contains 1 HRDC domain
Compartment
- nucleus, nucleolus
- irradiation leads to translocation of WRN from nucleoli to nucleoplasm
- PML regulates irradiation-induced WRN relocation
Pathology
- defects in WRN are a cause of
More general terms
Additional terms
References
- ↑ Yu CE et al Positional cloning of the Werner's syndrome gene Science 1996, 272:258-62 PMID: https://pubmed.ncbi.nlm.nih.gov/8602509
- ↑ Matsumoto T et al Impaired nuclear localization of defective DNA helicases in Werner's syndrome. Nature Genetics 1997, 16:335-6 PMID: https://pubmed.ncbi.nlm.nih.gov/9241267
- ↑ Gray et al The Werner syndrome protein is a DNA helicase Nature Genetics 1997 17:100-3 PMID: https://pubmed.ncbi.nlm.nih.gov/9288107
- ↑ UniProt http://www.uniprot.org/uniprot/Q14191.html
- ↑ WRN; Note: WRN mutation db (Warner disease) http://www.pathology.washington.edu/werner/ws_wrn.html
- ↑ Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/WRNID284.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=WRN
- ↑ NIEHS-SNPs http://egp.gs.washington.edu/data/wrn/
- ↑ UniProt PubMed refs
PMID: https://pubmed.ncbi.nlm.nih.gov/17563354
PMID: https://pubmed.ncbi.nlm.nih.gov/563354
PMID: https://pubmed.ncbi.nlm.nih.gov/19283071
PMID: https://pubmed.ncbi.nlm.nih.gov/283071
PMID: https://pubmed.ncbi.nlm.nih.gov/21639834
PMID: https://pubmed.ncbi.nlm.nih.gov/11863428
PMID: https://pubmed.ncbi.nlm.nih.gov/863428
PMID: https://pubmed.ncbi.nlm.nih.gov/17961633
PMID: https://pubmed.ncbi.nlm.nih.gov/961633
PMID: https://pubmed.ncbi.nlm.nih.gov/20159463
PMID: https://pubmed.ncbi.nlm.nih.gov/159463
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7486
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7486
- OMIM: https://mirror.omim.org/entry/114500
- OMIM: https://mirror.omim.org/entry/277700
- OMIM: https://mirror.omim.org/entry/604611
- UniProt: http://www.uniprot.org/uniprot/Q14191.html