Involvement of DNA polymerase mu in the repair of a specific subset of DNA double-strand breaks in mammalian cells.
Involvement of DNA polymerase mu in the repair of a specific subset of DNA double-strand breaks in mammalian cells.
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DNA聚合酶MU参与哺乳动物细胞中DNA双链断裂的特定子集的修复。
DOI：
10.1093/nar/gkm243
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发表时间：
2007
影响因子：
14.9
通讯作者：
Canitrot, Yvan
中科院分区：
文献类型：
--
作者：
Capp, Jean-Pascal;Boudsocq, Francois;Besnard, Anne-Gaelle;Lopez, Bernard S;Cazaux, Christophe;Hoffmann, Jean-Sebastien;Canitrot, Yvan
DNA双链断裂（DSB）的修复需要处理断裂的末端以完成连接过程。最近的研究表明，DNA聚合酶μ（polμ）和DNA聚合酶λ（polλ）都参与了体外非同源末端连接过程。然而，在polμ和/或polλ缺陷的动物模型中未观察到表型。这样的观察结果可能是由于DNA聚合酶X家族共享的功能冗余。为了避免这种冗余并阐明polμ在末端连接过程中的作用，我们产生了过表达野生型以及polμ的失活形式（polμD）的细胞。我们观察到，当polμ或polμD过表达时，细胞对电离辐射（IR）的敏感性增加。然而，仅在表达polμD的细胞中，对IR反应的遗传不稳定性增加。此外，对I-SceI诱导的DNA DSB的染色体内修复的分析没有显示polμ或polμD表达对粘性末端和部分互补末端的连接效率的任何影响。最后，当polμ或polμD过表达时，修复末端的序列受到特异性影响，这支持了polμ可能参与DSB子集修复的假设，当连接的解析需要一些间隙填充时。
The repair of DNA double-strand breaks (DSB) requires processing of the broken ends to complete the ligation process. Recently, it has been shown that DNA polymerase μ (polμ) and DNA polymerase λ (polλ) are both involved in such processing during non-homologous end joining in vitro. However, no phenotype was observed in animal models defective for either polμ and/or polλ. Such observations could result from a functional redundancy shared by the X family of DNA polymerases. To avoid such redundancy and to clarify the role of polμ in the end joining process, we generated cells over-expressing the wild type as well as an inactive form of polμ (polμD). We observed that cell sensitivity to ionizing radiation (IR) was increased when either polμ or polμD was over-expressed. However, the genetic instability in response to IR increased only in cells expressing polμD. Moreover, analysis of intrachromosomal repair of the I-SceI-induced DNA DSB, did not reveal any effect of either polμ or polμD expression on the efficiency of ligation of both cohesive and partially complementary ends. Finally, the sequences of the repaired ends were specifically affected when polμ or polμD was over-expressed, supporting the hypothesis that polμ could be involved in the repair of a DSB subset when resolution of junctions requires some gap filling.