Mouse DNA polymerase kappa has a functional role in the repair of DNA strand breaks.
Mouse DNA polymerase kappa has a functional role in the repair of DNA strand breaks.
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DOI：
10.1016/j.dnarep.2013.02.008
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发表时间：
2013-05-01
期刊：
影响因子：
3.8
通讯作者：
Guo, Caixia
中科院分区：
文献类型：
--
作者：
Zhang, Xiuli;Lv, Lingna;Chen, Qian;Yuan, Fenghua;Zhang, Ting;Yang, Yeran;Zhang, Hui;Wang, Yun;Jia, Yan;Qian, Liangyue;Chen, Benjamin;Zhang, Yanbin;Friedberg, Errol C.;Tang, Tie-Shan;Guo, Caixia
y家族的DNA聚合酶支持翻译DNA合成（TLS）与DNA损伤导致的DNA复制停滞相关。最近，一些研究表明，一些特殊的TLS聚合酶也支持体内TLS以外的DNA代谢的其他方面。在这里，我们发现小鼠聚合酶kappa （Polκ）可以像聚合酶eta和iota一样在体内激光诱导的损伤部位积累。募集是通过含有rna相互作用肽、泛素锌指基序2和核定位信号的Polκ c末端介导的。有趣的是，这种募集在msh2缺失的LoVo细胞和rad18缺失的细胞中显著减少。我们进一步观察到polκ -缺陷小鼠胚胎成纤维细胞对H2O2处理异常敏感，单链断裂修复和双链断裂修复均存在缺陷。我们推测Polκ可能在体内氧化应激后的链断裂修复中起重要作用。
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.
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