Overexpression of Rad51 protein stimulates homologous recombination and increases resistance of mammalian cells to ionizing radiation
Overexpression of Rad51 protein stimulates homologous recombination and increases resistance of mammalian cells to ionizing radiation
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DOI：
10.1093/nar/26.12.2859
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发表时间：
1998-06-15
影响因子：
14.9
通讯作者：
Defais, M
中科院分区：
文献类型：
--
作者：
Vispé, S;Cazaux, C;Defais, M
Rad 51蛋白与细菌重组酶RecA具有结构和功能同源性。人Rad 51（HsRad 51）能够在体外催化同源DNA分子之间的链交换。然而，Rad 51在哺乳动物中的生物学功能在很大程度上是未知的。为了解决这个问题，我们克隆了仓鼠Rad 51 cDNA，并在CHO细胞中过表达相应的蛋白。我们发现，2-3倍过表达的蛋白质刺激整合基因之间的同源重组20倍，表明Rad 51是一个功能和关键酶的染色体内重组途径。过表达Rad 51的细胞在S/G（2）期受到电离辐射后对辐射有抵抗作用。这表明，Rad 51参与修复双链断裂最有可能通过同源重组涉及姐妹染色单体后形成的S期。
Rad51 proteins share both structural and functional homologies with the bacterial recombinase RecA. The human Rad51 (HsRad51) is able to catalyse strand exchange between homologous DNA molecules in vitro. However the biological functions of Rad51 in mammals are largely unknown. In order to address this question, we have cloned hamster Rad51 cDNA and overexpressed the corresponding protein in CHO cells. We found that 2-3-fold overexpression of the protein stimulated the homologous recombination between integrated genes by 20-fold indicating that Rad51 is a functional and key enzyme of an intrachromosomal recombination pathway. Cells overexpressing Rad51 were resistant to ionizing radiation when irradiated in late S/G(2) phase of the cell cycle. This suggests that Rad51 participate in the repair of double-strand breaks most likely by homologous recombination involving sister chromatids formed after the S phase.