RecBCD is required to complete chromosomal replication: Implications for double-strand break frequencies and repair mechanisms.
RecBCD is required to complete chromosomal replication: Implications for double-strand break frequencies and repair mechanisms.
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DOI：
10.1016/j.dnarep.2015.04.018
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发表时间：
2015-08
期刊：
影响因子：
3.8
通讯作者：
Courcelle CT
中科院分区：
文献类型：
--
作者：
Courcelle J;Wendel BM;Livingstone DD;Courcelle CT
同源双链断裂修复机制的几个方面仍不清楚。尽管人们已经集中精力研究重组反应是如何开始的，但对随后发生的分子事件所知甚少。基于生物化学研究，目前的模型认为RecBCD处理双链末端并装载RecA启动重组修复。然而，最近的研究表明，RecBCD通过不涉及RecA或重组的机制在完成染色体上的复制事件中起关键作用。在这里，我们检查了几项早期和最近的研究，这些研究表明RecBCD也在重组过程的后期起作用-在起始，链侵入和交叉分解发生之后。类似于它在完成复制中的作用，我们提出了一个模型，在这个模型中，在断裂分子上缺失的序列被修复的地方，需要RecBCD来切除和解决与同源重组相关的DNA合成。我们解释了在recBC和recD突变体中完成染色体复制的能力受损如何可能解释了这些突变体中生存能力丧失和基因组不稳定的原因，并得出结论，自发双链断裂和复制叉崩溃的发生频率远低于之前的推测。
Several aspects of the mechanism of homologous double strand break repair remain unclear. Although intensive efforts have focused on how recombination reactions initiate, far less is known about the molecular events that follow. Based upon biochemical studies, current models propose that RecBCD processes double strand ends and loads RecA to initiate recombinational repair. However, recent studies have shown that RecBCD plays a critical role in completing replication events on the chromosome through a mechanism that does not involve RecA or recombination. Here, we examine several studies, both early and recent, that suggest RecBCD also operates late in the recombination process- after initiation, strand invasion, and crossover resolution have occurred. Similar to its role in completing replication, we propose a model in which RecBCD is required to resect and resolve the DNA synthesis associated with homologous recombination at the point where the missing sequences on the broken molecule have been restored. We explain how the impaired ability to complete chromosome replication in recBC and recD mutants is likely to account for the loss of viability and genome instability in these mutants, and conclude that spontaneous double strand breaks and replication fork collapse occur far less frequently than previously speculated.