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Werner syndrome ATP-dependent helicase (WRN, RECQ3, RECQL2)

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 Cofactor: - binds 2 Mg+2 per subunit - high activity with Mn+2 & Zn+2 (in vitro) 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 a) Werner syndrome (WRN) b) colorectal carcinoma

Related

Werner syndrome WRN (Werner's syndrome) gene

General

helicase (DNA unwinding protein, DNA untwisting protein) human longevity protein phosphoprotein

Properties

SIZE: entity length = 1432 aa MW = 162 kD COMPARTMENT: cell nucleus MOTIF: acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl WRNIP1 interaction {2-277} 3'-5' exonuclease {60-228} MOTIF: Mg+2-binding site SITE: 82-82 Mg+2-binding site SITE: 84-84 tryptophan residue {145} Mg+2-binding site SITE: 216-216 repeats {424-477} MOTIF: consensus repeat {424-450} Ser phosphorylation site {S426} Ser phosphorylation site {S440} consensus repeat {451-477} Ser phosphorylation site {S453} Ser phosphorylation site {S467} glutamate-rich region {507-510} MOTIF: glutamate residue (SEVERAL) helicase NAME: helicase SITE: 558-724 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 571-578 DEAD/H box NAME: DEAD/H box SITE: 668-671 Helicase {749-899} DNA interaction {987-993} phenylalanine residue {1037} Ser phosphorylation site {S1133} HRDC {1150-1229}

Database Correlations

OMIM correlations MORBIDMAP 604611 UniProt Q14191 PFAM correlations Entrez Gene 7486 Kegg hsa:7486 ENZYME 3.6.4.12

References

  1. Yu CE et al Positional cloning of the Werner's syndrome gene Science 1996, 272:258-62 PMID: 8602509
  2. Matsumoto T et al Impaired nuclear localization of defective DNA helicases in Werner's syndrome. Nature Genetics 1997, 16:335-6 PMID: 9241267
  3. Gray et al The Werner syndrome protein is a DNA helicase Nature Genetics 1997 17:100-3 PMID: 9288107
  4. UniProt :accession Q14191
  5. WRN; Note: WRN mutation db (Warner disease) http://www.pathology.washington.edu/werner/ws_wrn.html
  6. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/WRNID284.html
  7. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=WRN
  8. NIEHS-SNPs http://egp.gs.washington.edu/data/wrn/
  9. UniProt PubMed refs - PMID: 17563354 - PMID: 563354 - PMID: 19283071 - PMID: 283071 - PMID: 21639834 - PMID: 11863428 - PMID: 863428 - PMID: 17961633 - PMID: 961633 - PMID: 20159463 - PMID: 159463