Mrc1 and Srs2 are major actors in the regulation of spontaneous crossover
Mrc1 and Srs2 are major actors in the regulation of spontaneous crossover
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DOI：
10.1038/sj.emboj.7601158
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发表时间：
2006-06-21
期刊：
影响因子：
11.4
通讯作者：
Gangloff, Serge
中科院分区：
文献类型：
--
作者：
Robert, Thomas;Dervins, Delphine;Gangloff, Serge
在营养细胞中，大多数重组中间产物的代谢与交叉(CO)无关。避免CoS允许修复和防止基因组重排，如果所涉及的序列位于异位位置，则可能是有害的。我们设计了一个系统，允许在酿酒酵母中筛选自发的基因内重组事件，并研究不同遗传背景下的CO结果。我们分析了在没有srs2和sgs1解旋酶、DNA损伤检查点蛋白以及突变的增殖细胞核抗原(PCNA)的情况下的CO结果，发现它们都有助于基因组的稳定性。对Cos的显著影响是由srs2 Delta、mrc1 Delta和增殖细胞核抗原中pol30-RR突变介导的。我们的结果支持了这样的观点，即MRc1在DNA复制中发挥着特定的作用，促进了srs2向增殖细胞核抗原的募集，而不依赖于检查点信号。Srs2将防止双Holliday结(DHJ)的形成，从而防止CO的形成。SGS1也负向调节CO的形成，但通过不同的过程将dHJ分解为非CO产物。
In vegetative cells, most recombination intermediates are metabolized without an association with a crossover ( CO). The avoidance of COs allows for repair and prevents genomic rearrangements, potentially deleterious if the sequences involved are at ectopic locations. We have designed a system that permits to screen spontaneous intragenic recombination events in Saccharomyces cerevisiae and to investigate the CO outcome in different genetic contexts. We have analyzed the CO outcome in the absence of the Srs2 and Sgs1 helicases, DNA damage checkpoint proteins as well as in a mutant proliferating cell nuclear antigen ( PCNA) and found that they all contribute to genome stability. Remarkably high effects on COs are mediated by srs2 Delta, mrc1 Delta and a pol30-RR mutation in PCNA. Our results support the view that Mrc1 plays a specific role in DNA replication, promoting the Srs2 recruitment to PCNA independently of checkpoint signaling. Srs2 would prevent formation of double Holliday junctions ( dHJs) and thus CO formation. Sgs1 also negatively regulates CO formation but through a different process that resolves dHJs to yield non-CO products.