Institut Curie-Centre National de la Recherche Scientifique, UMR3348, Réponse Cellulaire aux Perturbations de la Réplication, Université Paris-Sud XI, Orsay, France.
Mol Cell. 2010 Aug 13;39(3):346-59. doi: 10.1016/j.molcel.2010.07.015.
Template switching induced by stalled replication forks has recently been proposed to underlie complex genomic rearrangements. However, the resulting models are not supported by robust physical evidence. Here, we analyzed replication and recombination intermediates in a well-defined fission yeast system that blocks replication forks. We show that, in response to fork arrest, chromosomal rearrangements result from Rad52-dependent nascent strand template exchange occurring during fork restart. This template exchange occurs by both Rad51-dependent and -independent mechanisms. We demonstrate that Rqh1, the BLM homolog, limits Rad51-dependent template exchange without affecting fork restart. In contrast, we report that the Srs2 helicase promotes both fork restart and template exchange. Our data demonstrate that template exchange occurs during recombination-dependent fork restart at the expense of genome rearrangements.
模板切换诱导停滞的复制叉最近被提议作为复杂基因组重排的基础。然而，由此产生的模型并没有得到可靠的物理证据的支持。在这里，我们在一个明确的裂殖酵母系统中分析了复制和重组中间体，该系统可以阻断复制叉。我们表明，在复制叉停滞的情况下，染色体重排是由于在叉重新启动期间发生的 Rad52 依赖性新生链模板交换引起的。这种模板交换通过 Rad51 依赖性和非依赖性机制发生。我们证明，BLM 同源物 Rqh1 限制 Rad51 依赖性模板交换而不影响叉重新启动。相比之下，我们报告说 Srs2 解旋酶促进叉重新启动和模板交换。我们的数据表明，模板交换发生在依赖重组的叉重新启动期间，代价是基因组重排。
