The Saccharomyces cerevisiae Sae2 protein promotes resection and bridging of double strand break ends
The Saccharomyces cerevisiae Sae2 protein promotes resection and bridging of double strand break ends
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DOI：
10.1074/jbc.m508339200
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发表时间：
2005-11-18
影响因子：
4.8
通讯作者：
Longhese, MP
中科院分区：
文献类型：
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作者：
Clerici, M;Mantiero, D;Longhese, MP
当真核生物染色体发生双链断裂（DSB）时，几种进化上保守的蛋白质（其中包括MRX复合物）被募集到断裂位点，导致检查点激活和DNA修复。已知酿酒酵母Sae 2蛋白在减数分裂DSB加工和特定有丝分裂DSB修复事件中与MRX复合物一起工作，其功能仅开始阐明。在这里，我们提供了新的见解Sae 2在有丝分裂DSB修复的作用。我们表明，修复单链退火的一个单一的DSB，这是由HO核酸内切酶之间的直接重复，是有缺陷的Sae 2的情况下，并在存在的亚纯型rad 50 s等位基因改变Rad 50亚基的MRX。此外，SAE 2过表达部分抑制了rad 50单链退火修复缺陷，表明后者可能是由缺陷的MRX-Sae 2相互作用引起的。最后，SAE 2缺失减慢HO诱导的DSB的切除并损害DSB末端桥接。因此，Sae 2通过确保断裂末端的切除和染色体内缔合参与DSB单链退火修复。
When eukaryotic chromosomes undergo double strand breaks (DSBs), several evolutionarily conserved proteins, among which the MRX complex, are recruited to the break site, leading to checkpoint activation and DNA repair. The function of the Saccharomyces cerevisiae Sae2 protein, which is known to work together with the MRX complex in meiotic DSB processing and in specific mitotic DSB repair events, is only beginning to be elucidated. Here we provide new insights into the role of Sae2 in mitotic DSB repair. We show that repair by single strand annealing of a single DSB, which is generated by the HO endonuclease between direct repeats, is defective both in the absence of Sae2 and in the presence of the hypomorphic rad50s allele altering the Rad50 subunit of MRX. Moreover, SAE2 overexpression partially suppresses the rad50s single strand annealing repair defects, suggesting that the latter might arise from defective MRX-Sae2 interactions. Finally, SAE2 deletion slows down resection of an HO-induced DSB and impairs DSB end bridging. Thus, Sae2 participates in DSB single strand annealing repair by ensuring both resection and intrachromosomal association of the broken ends.