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首页> 外文期刊>Cell cycle >Importance of the cell cycle phase for the choice of the appropriate DSB repair pathway, for genome stability maintenance: the trans-S double-strand break repair model.
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Importance of the cell cycle phase for the choice of the appropriate DSB repair pathway, for genome stability maintenance: the trans-S double-strand break repair model.

机译：细胞周期阶段对于选择合适的DSB修复途径，维持基因组稳定性的重要性：trans-S双链断裂修复模型。

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摘要

A DNA double-strand break (DSB) is a highly harmful lesion that can lead to genome rearrangements. Two main pathways compete for DSB repair: homologous recombination (HR) and nonhomologous end-joining (NHEJ). Depending on the cell cycle phase, the choice of one DSB repair pathway over the other will secure genome stability maintenance or in contrast will increase the risk of genetic instability. HR with the sister chromatid is an efficient way to maintain genome stability, for damage occurring at a post-replication stage. However, in G(1) checkpoint-defective cells, DSBs produced in the G(1) phase and not repaired by NHEJ, can progress through S phase and be processed by HR in late S/G(2) phase. We propose the "trans-S DSB repair" model to account for these data. In this situation HR cannot use the sister chromatid (which is also broken at the same locus) and is thus forced to use ectopic homologous sequences dispersed through the genome, increasing the risk of genetic instability. This shows that the two DSB repair pathways can compete through the cell cycle and underlines the importance of the association between the cell cycle checkpoint and the appropriate DNA repair pathway for genome stability maintenance.
机译：DNA双链断裂（DSB）是一种高度有害的病变，可导致基因组重排。竞争DSB修复的两个主要途径是：同源重组（HR）和非同源末端连接（NHEJ）。取决于细胞周期阶段，选择一种DSB修复途径而不是另一种途径将确保维持基因组稳定性，或者相反会增加遗传不稳定的风险。姊妹染色单体的HR是维持基因组稳定性的有效方法，可防止复制后阶段发生损伤。但是，在G（1）检查点缺陷细胞中，DSB在G（1）阶段产生且未被NHEJ修复，可以前进到S阶段，并在S / G（2）后期由HR处理。我们提出“ trans-S DSB修复”模型来解决这些数据。在这种情况下，HR无法使用姐妹染色单体（在同一位点也被破坏），因此被迫使用分散在基因组中的异位同源序列，从而增加了遗传不稳定的风险。这表明两个DSB修复途径可以在细胞周期中竞争，并且强调了细胞周期检查点与适当的DNA修复途径之间的关联对于基因组稳定性维持的重要性。

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