Poly(ADP-ribose) polymerase (PARP-1) has a controlling role in homologous recombination
Poly(ADP-ribose) polymerase (PARP-1) has a controlling role in homologous recombination
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DOI：
10.1093/nar/gkg703
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发表时间：
2003-09-01
影响因子：
14.9
通讯作者：
Helleday, T
中科院分区：
文献类型：
--
作者：
Schultz, N;Lopez, E;Helleday, T
具有非功能性聚（adp -核糖）聚合酶（PARP-1）的细胞显示姐妹染色单体交换水平增加，表明这些细胞存在超重组表型。为了进一步研究PARP-1在同源重组（HR）中的作用，我们研究了PARP-1如何影响核HR位点（Rad51焦点）和内切酶诱导的DNA双链断裂（DSB）的HR修复。一些与HR相关的蛋白定位于Rad51病灶，而HR缺陷细胞在DNA损伤的反应中不能形成Rad51病灶。在这里，我们发现PARP-1主要不定位于Rad51病灶，Rad51病灶在PARP-1（-/-）细胞中形成，也是对羟基脲的反应。此外，我们发现在parp -1抑制的细胞中，诱导位点特异性DSB后的同源定向修复是正常的。相反，PARP-1的抑制或缺失增加了自发的Rad51病灶形成，证实了这些细胞中的超重组表型。我们的数据表明，PARP-1控制着HR识别的DNA损伤，而它并不参与HR的执行。
Cells with non-functional poly(ADP-ribose) polymerase (PARP-1) show increased levels of sister chromatid exchange, suggesting a hyper recombination phenotype in these cells. To further investigate the involvement of PARP-1 in homologous recombination (HR) we investigated how PARP-1 affects nuclear HR sites (Rad51 foci) and HR repair of an endonuclease-induced DNA double-strand break (DSB). Several proteins involved in HR localise to Rad51 foci and HR-deficient cells fail to form Rad51 foci in response to DNA damage. Here, we show that PARP-1 mainly does not localise to Rad51 foci and that Rad51 foci form in PARP-1(-/-) cells, also in response to hydroxyurea. Furthermore, we show that homology directed repair following induction of a site-specific DSB is normal in PARP-1-inhibited cells. In contrast, inhibition or loss of PARP-1 increases spontaneous Rad51 foci formation, confirming a hyper recombination phenotype in these cells. Our data suggest that PARP-1 controls DNA damage recognised by HR and that it is not involved in executing HR as such.