title: Mouse DNA polymerase kappa has a functional role in the repair of DNA strand breaks.
abstract: The Y-family of DNA polymerases support of translesion DNA synthesis (TLS) associated with stalled DNA replication by DNA damage. Recently, a number of studies suggest that some specialized TLS polymerases also support other aspects of DNA metabolism beyond TLS in vivo. Here we show that mouse polymerase kappa (Polκ) could accumulate at laser-induced sites of damage in vivo resembling polymerases eta and iota. The recruitment was mediated through Polκ C-terminus which contains the PCNA-interacting peptide, ubiquitin zinc finger motif 2 and nuclear localization signal. Interestingly, this recruitment was significantly reduced in MSH2-deficient LoVo cells and Rad18-depleted cells. We further observed that Polκ-deficient mouse embryo fibroblasts were abnormally sensitive to H2O2 treatment and displayed defects in both single-strand break repair and double-strand break repair. We speculate that Polκ may have an important role in strand break repair following oxidative stress in vivo.
authors.affiliation: Laboratory of Cancer Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.forename: Lingna
authors.initials: L
authors.lastname: Lv
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Fenghua
authors.initials: F
authors.lastname: Yuan
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Yeran
authors.initials: Y
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Jia
authors.forename: Liangyue
authors.initials: L
authors.lastname: Qian
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chen
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Errol C
authors.initials: EC
authors.lastname: Friedberg
authors.forename: Tie-Shan
authors.initials: TS
authors.lastname: Tang
authors.forename: Caixia
authors.initials: C
authors.lastname: Guo
mesh_terms: D000818:Animals; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007834:Lasers; D051379:Mice; D018345:Mice, Knockout; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D019913:Nuclear Localization Signals; D018384:Oxidative Stress; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017434:Protein Structure, Tertiary; D000099270:Y-Family DNA Polymerases
chemical_list: D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; D006861:Hydrogen Peroxide; D051718:MutS Homolog 2 Protein; D019913:Nuclear Localization Signals; D018809:Proliferating Cell Nuclear Antigen; C485953:Rad18 protein, mouse; C498613:Polk protein, mouse; D000099270:Y-Family DNA Polymerases; C497173:Msh2 protein, mouse