Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair.
Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair.
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DOI：
10.1093/nar/gkn971
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发表时间：
2009-02
影响因子：
14.9
通讯作者：
Helleday T
中科院分区：
文献类型：
--
作者：
Savolainen L;Helleday T
先前已表明转录极大地增强了哺乳动物细胞中的重组。然而，参与催化这一过程的蛋白质以及参与转录相关重组（TAR）的重组途径仍然未知。众所周知，BRCA2 蛋白和 RAD51 旁系同源蛋白 XRCC2 都是同源重组所必需的。在这里，我们表明 BRCA2 蛋白也是 TAR 所必需的，而 XRCC2 蛋白不参与。 XRCC2 突变的 irs1 细胞中 XRCC2 基因的表达可恢复 I-SceI 诱导的 DNA 双链断裂的同源重组修复缺陷，而 TAR 不受影响。有趣的是，XRCC2 缺陷的 irs1 细胞也擅长在缓慢的复制叉处诱导重组，这表明 TAR 在机制上与这种重组途径相关。总之，我们表明 TAR 依赖于 BRCA2，但独立于 XRCC2，并且该重组途径与用于修复两端 DNA 双链断裂的途径是分开的。
It has previously been shown that transcription greatly enhances recombination in mammalian cells. However, the proteins involved in catalysing this process and the recombination pathways involved in transcription-associated recombination (TAR) are still unknown. It is well established that both the BRCA2 protein and the RAD51 paralog protein XRCC2 are required for homologous recombination. Here, we show that the BRCA2 protein is also required for TAR, while the XRCC2 protein is not involved. Expression of the XRCC2 gene in XRCC2 mutated irs1 cells restores the defect in homologous recombination repair of an I-SceI-induced DNA double-strand break, while TAR is unaffected. Interestingly, the XRCC2-deficient irs1 cells are also proficient in recombination induced at slowed replication forks, suggesting that TAR is mechanistically linked with this recombination pathway. In conclusion, we show that TAR depends on BRCA2 but is independent of XRCC2, and that this recombination pathway is separate from that used to repair a two-ended DNA double-strand break.
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