Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination
Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination
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作者：
Johnson, RD;Liu, N;Jasin, M
DNA双链断裂的修复对于细胞维持其基因组完整性至关重要。两种主要机制负责修复哺乳动物细胞中的这些断裂，非同源末端连接（NHEJ）和同源重组（HR）（1，2）：前者在哺乳动物细胞中的重要性已得到充分证实（3），而后者的作用才刚刚出现，同源重组可能是由一组进化上保守的基因促进的，称为Rad 52上位性（4-11）。HR途径的一个重要组成部分是组链交换蛋白，在细菌中称为RecA（8）或在酵母中称为Rad 51（6）。基于与酵母Rad 51的序列同源性，几种哺乳动物基因涉及通过同源重组进行的修复（参考文献11）：其中之一是人XRCC 2（参考文献12，13）。在这里，我们表明，XRCC 2是必要的有效修复DNA双链断裂的姐妹染色单体之间的同源重组，我们发现，在XRCC 2缺陷的仓鼠细胞表现出超过100倍的下降，由双链断裂诱导的HR相比，亲本细胞系。通过用表达XRCC 2的质粒瞬时转染，该缺陷被校正至几乎野生型水平。XRCC 2突变细胞中的修复缺陷似乎仅限于重组修复，因为NHEJ是正常的。我们的结论是，XRCC 2参与修复DNA双链断裂的同源重组。
The repair of DNA double-strand breaks is essential for cells to maintain their genomic integrity. Two major mechanisms are responsible for repairing these breaks in mammalian cells, nonhomologous end-joining (NHEJ) and homologous recombination (HR)(1,2): the importance of the former in mammalian cells is well established(3), whereas the role of the latter is just emerging, Homologous recombination is presumably promoted by an evolutionarily conserved group of genes termed the Rad52 epistasis (4-11). An essential component of the HR pathway is the group strand-exchange protein, known as RecA in bacteria(8) or Rad51 in yeast(6). Several mammalian genes have been implicated in repair by homologous recombination on the basis of their sequence homology to yeast Rad51 (ref. 11): one of these is human XRCC2 (refs 12, 13). Here we show that XRCC2 is essential for the efficient repair of DNA double-strand breaks by homologous recombination between sister chromatids, We find that hamster cells deficient in XRCC2 show more than a 100-fold decrease in HR induced by double-strand breaks compared with the parental cell line. This defect is corrected to almost wild-type levels by transient transfection with a plasmid expressing XRCC2. The repair defect in XRCC2 mutant cells appears to be restricted to recombinational repair because NHEJ is normal. We conclude that XRCC2 is involved in the repair of DNA double-strand breaks by homologous recombination.