Savolainen Linda, Helleday Thomas
Department of Genetics, Microbiology and Toxicology, Arrhenius Laboratory, Stockholm University, S-106 91 Stockholm, Sweden.
Nucleic Acids Res. 2009 Feb;37(2):405-12. doi: 10.1093/nar/gkn971. Epub 2008 Nov 29.
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.
先前的研究表明，转录可极大地增强哺乳动物细胞中的重组。然而，催化这一过程的蛋白质以及转录相关重组（TAR）所涉及的重组途径仍然未知。众所周知，同源重组需要BRCA2蛋白和RAD51旁系同源蛋白XRCC2。在此，我们表明TAR也需要BRCA2蛋白，而XRCC2蛋白不参与其中。在XRCC2突变的irs1细胞中表达XRCC2基因可恢复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，缺乏XRCC2的irs1细胞在复制叉减慢时诱导的重组方面也很 proficient，这表明TAR在机制上与该重组途径相关。总之，我们表明TAR依赖于BRCA2但独立于XRCC2，并且这种重组途径与用于修复两端DNA双链断裂的途径不同。
