Role of mammalian RAD51L2 (RAD51C) in recombination and genetic stability
Role of mammalian RAD51L2 (RAD51C) in recombination and genetic stability
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DOI：
10.1074/jbc.m201402200
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发表时间：
2002-05-31
影响因子：
4.8
通讯作者：
Thacker, J
中科院分区：
文献类型：
--
作者：
French, CA;Masson, JY;Thacker, J
高度保守的RAD51蛋白在同源重组中起着核心作用。已经在哺乳动物细胞中发现了五个新的RAD51样基因，但对它们的功能知之甚少。对DNA损伤敏感的仓鼠细胞系irs3被发现存在RAD51L2基因突变和检测不到的RAD51L2蛋白水平。人类RAD51L2基因的表达显著增加了irs3对DNA损伤剂的抗性，但其他类似RAD51的基因或RAD51本身并不能增加IRS3对DNA损伤剂的抗性。与RAD51L2在同源重组中的作用一致，irs3细胞与野生型细胞相比，姐妹染色单体交换减少，等色单体断裂增加，损伤依赖的RAD51焦点形成减少。正如最近在人类细胞中证明的那样，我们表明RAD51L2形成了两个独立的仓鼠RAD51样蛋白复合体的一部分。值得注意的是，在irs3细胞中都没有形成RAD51样蛋白的复合体。我们的结果表明，RAD51L2在哺乳动物RAD51依赖的过程中发挥关键作用，这取决于参与同源重组修复的蛋白质复合体的形成。
The highly conserved RAD51 protein has a central role in homologous recombination. Five novel RAD51-like genes have been identified in mammalian cells, but little is known about their functions. A DNA damage-sensitive hamster cell line, irs3, was found to have a mutation in the RAD51L2 gene and an undetectable level of RAD51L2 protein. Resistance of irs3 to DNA-damaging agents was significantly increased by expression of the human RAD51L2 gene, but not by other RAD51-like genes or RAD51 itself. Consistent with a role for RAD51L2 in homologous recombination, irs3 cells show a reduction in sister chromatid exchange, an increase in isochromatid breaks, and a decrease in damage-dependent RAD51 focus formation compared with wild type cells. As recently demonstrated for human cells, we show that RAD51L2 forms part of two separate complexes of hamster RAD51-like proteins. Strikingly, neither complex of RAD51-like proteins is formed in irs3 cells. Our results demonstrate that RAD51L2 has a key role in mammalian RAD51-dependent processes, contingent on the formation of protein complexes involved in homologous recombination repair.