CNRS, UMR 8200, Institut de Cancérologie Gustave Roussy, Équipe Labélisée, Université Paris-Sud, «LIGUE 2014» Villejuif, France.
Institut Curie, CNRS, UMR 3348 Orsay, France.
Front Genet. 2014 Jun 11;5:175. doi: 10.3389/fgene.2014.00175. eCollection 2014.
Homologous recombination (HR) is an evolutionarily conserved process that plays a pivotal role in the equilibrium between genetic stability and diversity. HR is commonly considered to be error-free, but several studies have shown that HR can be error-prone. Here, we discuss the actual accuracy of HR. First, we present the product of genetic exchanges (gene conversion, GC, and crossing over, CO) and the mechanisms of HR during double strand break repair and replication restart. We discuss the intrinsic capacities of HR to generate genome rearrangements by GC or CO, either during DSB repair or replication restart. During this process, abortive HR intermediates generate genetic instability and cell toxicity. In addition to genome rearrangements, HR also primes error-prone DNA synthesis and favors mutagenesis on single stranded DNA, a key DNA intermediate during the HR process. The fact that cells have developed several mechanisms protecting against HR excess emphasize its potential risks. Consistent with this duality, several pro-oncogenic situations have been consistently associated with either decreased or increased HR levels. Nevertheless, this versatility also has advantages that we outline here. We conclude that HR is a double-edged sword, which on one hand controls the equilibrium between genome stability and diversity but, on the other hand, can jeopardize the maintenance of genomic integrity. Therefore, whether non-homologous end joining (which, in contrast with HR, is not intrinsically mutagenic) or HR is the more mutagenic process is a question that should be re-evaluated. Both processes can be "Dr. Jekyll" in maintaining genome stability/variability and "Mr. Hyde" in jeopardizing genome integrity.
同源重组（HR）是一种进化上保守的过程，在遗传稳定性和多样性之间的平衡中起着关键作用。HR 通常被认为是无错误的，但有几项研究表明 HR 也可能出错。在这里，我们讨论 HR 的实际准确性。首先，我们介绍了遗传交换（基因转换，GC 和交叉，CO）的产物以及双链断裂修复和复制启动过程中的 HR 机制。我们讨论了 HR 在双链断裂修复或复制启动过程中通过 GC 或 CO 产生基因组重排的内在能力。在此过程中，无效的 HR 中间体会产生遗传不稳定性和细胞毒性。除了基因组重排，HR 还启动易错的 DNA 合成，并有利于单链 DNA 上的突变，单链 DNA 是 HR 过程中的关键 DNA 中间产物。细胞已经开发出几种防止 HR 过度的机制，这一事实强调了其潜在的风险。与这一双重性一致，几种致癌情况一直与 HR 水平降低或升高有关。然而，这种多功能性也有我们在这里概述的优势。我们得出结论，HR 是一把双刃剑，一方面控制着基因组稳定性和多样性之间的平衡，但另一方面，也可能危及基因组完整性的维持。因此，非同源末端连接（与 HR 相反，非同源末端连接本质上不是诱变的）或 HR 哪个过程更具突变性是一个需要重新评估的问题。这两个过程都可以在维持基因组稳定性/可变性方面是“杰基尔博士”，在危及基因组完整性方面是“海德先生”。
