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Mouse DNA polymerase kappa has a functional role in the repair of DNA strand breaks
Authors:Xiuli Zhang  Lingna Lv  Qian Chen  Fenghua Yuan  Ting Zhang  Yeran Yang  Hui Zhang  Yun Wang  Yan Jia  Liangyue Qian  Benjamin Chen  Yanbin Zhang  Errol C. Friedberg  Tie-Shan Tang  Caixia Guo
Affiliation:1. Laboratory of Cancer Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China;2. State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;3. Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA;4. Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;5. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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.
Keywords:Polymerase kappa  PCNA  MSH2  Strand break repair  Laser micro-irradiation
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