The involvement of Srs2 in post-replication repair and homologous recombination in fission yeast
The involvement of Srs2 in post-replication repair and homologous recombination in fission yeast
复制标题
DOI：
10.1093/nar/gkh317
复制
发表时间：
2004-02-01
影响因子：
14.9
通讯作者：
Whitby, MC
中科院分区：
文献类型：
--
作者：
Doe, CL;Whitby, MC
同源重组对于修复双链断裂和子链缺口很重要，也有助于重新启动停滞和崩溃的复制叉子。然而，有时重组是不合适的，可能会产生有害的后果。为了缓和重组，细胞使用DNA解旋酶来解开联合DNA分子和/或将重组酶从DNA中解离。芽殖酵母srs2就是这样一种解旋酶。它可以通过解离RAD51核蛋白细丝发挥作用，是将DNA损伤引导到复制后修复(PRR)途径所必需的。在这里，我们研究了srs2在控制分裂酵母重组中的作用。与萌芽酵母相似，裂解酵母Srs2的缺失会导致对一系列DNA损伤剂、依赖于rhp51的超重组和合成疾病的超敏反应，当与rqh1(-)结合时，rqh1(-)可通过缺失rhp51、rhp55或rhp57来抑制。上位性分析表明，Srs2和结构特异性内切酶MUS81-Eme1在PRR的耐受/修复紫外线损伤的子途径中发挥作用。然而，与酿酒酵母不同的是，在裂殖酵母中，srs2不是将病变引导到PRR途径所必需的。除了作为一种抗重组酶外，我们还表明，srs2可以帮助重组修复喜树碱诱导的折叠复制叉，而不依赖于PRR。
Homologous recombination is important for the repair of double-strand breaks and daughter strand gaps, and also helps restart stalled and collapsed replication forks. However, sometimes recombination is inappropriate and can have deleterious consequences. To temper recombination, cells have employed DNA helicases that unwind joint DNA molecules and/or dissociate recombinases from DNA. Budding yeast Srs2 is one such helicase. It can act by dissociating Rad51 nucleoprotein filaments, and is required for channelling DNA lesions to the post-replication repair (PRR) pathway. Here we have investigated the role of Srs2 in controlling recombination in fission yeast. Similar to budding yeast, deletion of fission yeast srs2 results in hypersensitivity to a range of DNA damaging agents, rhp51-dependent hyper-recombination and synthetic sickness when combined with rqh1(-) that is suppressed by deleting rhp51, rhp55 or rhp57. Epistasis analysis indicates that Srs2 and the structure-specific endonuclease Mus81-Eme1 function in a sub-pathway of PRR for the tolerance/repair of UV-induced damage. However, unlike in Saccharomyces cerevisiae, Srs2 is not required for channelling lesions to the PRR pathway in Schizosaccharomyces pombe. In addition to acting as an antirecombinase, we also show that Srs2 can aid the recombinational repair of camptothecin-induced collapsed replication forks, independently of PRR.