title: WRN functions in a RAD18-dependent damage avoidance pathway.
abstract: Werner syndrome (WS), caused by mutations in a gene (WRN) that encodes a RecQ DNA helicase, is characterized by premature aging and cancer predisposition. Cells derived from WS patients show sensitivity to several DNA damaging agents. Previous studies revealed that the WRN protein plays roles in DNA repair or damage tolerance, although it was not yet assigned to a specific pathway. Here we examined the relationship between WRN and the post-replication repair protein RAD18 by generating deletion derivatives in chicken DT40 cells. The frequency of spontaneous sister chromatid exchange in WRN(-/-)/RAD18(-/-) double mutant cells was slightly increased compared to that of either single mutant. However, the sensitivity of WRN(-/-)/RAD18(-/-) cells to 4-nitroquinoline 1-oxide and methyl methanesulfonate was almost the same as that of RAD18(-/-) cells. Moreover, the cisplatin sensitivity of RAD18(-/-) cells was slightly suppressed by disruption of WRN. These data suggest that WRN functions in a pathway involving RAD18 under damage-inducing conditions.
authors.affiliation: Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Yu Peng
authors.initials: YP
authors.lastname: Dong
authors.forename: Masayuki
authors.initials: M
authors.lastname: Seki
authors.forename: Akari
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Eri
authors.initials: E
authors.lastname: Inoue
authors.forename: Shinya
authors.initials: S
authors.lastname: Furukawa
authors.forename: Shusuke
authors.initials: S
authors.lastname: Tada
authors.forename: Takemi
authors.initials: T
authors.lastname: Enomoto
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002645:Chickens; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D018274:Electroporation; D005090:Exodeoxyribonucleases; D018390:Gene Targeting; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D053484:RecQ Helicases / Q000235:genetics* / Q000378:metabolism*; D012854:Sister Chromatid Exchange; D044767:Ubiquitin-Protein Ligases; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism; D000071657:Werner Syndrome Helicase
chemical_list: D004268:DNA-Binding Proteins; D009153:Mutagens; D018809:Proliferating Cell Nuclear Antigen; C485954:RAD18 protein, human; D011838:Radiation-Sensitizing Agents; D015112:4-Nitroquinoline-1-oxide; D008741:Methyl Methanesulfonate; D044767:Ubiquitin-Protein Ligases; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; D002945:Cisplatin