RecG controls DNA amplification at double-strand breaks and arrested replication forks.
RecG controls DNA amplification at double-strand breaks and arrested replication forks.
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DOI：
10.1002/1873-3468.12583
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发表时间：
2017-04
期刊：
影响因子：
3.5
通讯作者：
Leach DRF
中科院分区：
文献类型：
--
作者：
Azeroglu B;Leach DRF
DNA扩增是一种强大的突变机制，是癌症和耐药性的标志。因此，了解细胞用来避免过度复制其基因组部分的基本途径非常重要。最近的研究表明，在不存在RecG的情况下，在DNA双链断裂修复（DSBR）和DNA复制停滞的位点处观察到DNA扩增，这些位点被加工以产生双链末端。RecG还在稳定DSBR期间形成的关节分子中起作用。我们认为RecG阻止了一种以前未被认识到的DNA扩增机制，我们称之为反向重启，该机制在重组形成的D环和被捕获的复制叉处不正确地加载复制解旋酶，从而产生DNA双链末端。
DNA amplification is a powerful mutational mechanism that is a hallmark of cancer and drug resistance. It is therefore important to understand the fundamental pathways that cells employ to avoid over‐replicating sections of their genomes. Recent studies demonstrate that, in the absence of RecG, DNA amplification is observed at sites of DNA double‐strand break repair (DSBR) and of DNA replication arrest that are processed to generate double‐strand ends. RecG also plays a role in stabilising joint molecules formed during DSBR. We propose that RecG prevents a previously unrecognised mechanism of DNA amplification that we call reverse‐restart, which generates DNA double‐strand ends from incorrect loading of the replicative helicase at D‐loops formed by recombination, and at arrested replication forks.