Morikawa Hirofumi, Morishita Takashi, Kawane Shiho, Iwasaki Hiroshi, Carr Antony M, Shinagawa Hideo
Department of Molecular Microbiology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Mol Cell Biol. 2004 Nov;24(21):9401-13. doi: 10.1128/MCB.24.21.9401-9413.2004.
Smc5 and Smc6 proteins form a heterodimeric SMC (structural maintenance of chromosome) protein complex like SMC1-SMC3 cohesin and SMC2-SMC4 condensin, and they associate with non-SMC proteins Nse1 and Nse2 stably and Rad60 transiently. This multiprotein complex plays an essential role in maintaining chromosome integrity and repairing DNA double strand breaks (DSBs). This study characterizes a Schizosaccharomyces pombe mutant rad62-1, which is hypersensitive to methyl methanesulfonate (MMS) and synthetically lethal with rad2 (a feature of recombination mutants). rad62-1 is hypersensitive to UV and gamma rays, epistatic with rhp51, and defective in repair of DSBs. rad62 is essential for viability and genetically interacts with rad60, smc6, and brc1. Rad62 protein physically associates with the Smc5-6 complex. rad62-1 is synthetically lethal with mutations in the genes promoting recovery from stalled replication, such as rqh1, srs2, and mus81, and those involved in nucleotide excision repair like rad13 and rad16. These results suggest that Rad62, like Rad60, in conjunction with the Smc5-6 complex, plays an essential role in maintaining chromosome integrity and recovery from stalled replication by recombination.
Smc5和Smc6蛋白形成一种异源二聚体SMC(染色体结构维持)蛋白复合物,类似于SMC1 - SMC3黏连蛋白和SMC2 - SMC4凝聚蛋白,并且它们与非SMC蛋白Nse1和Nse2稳定结合,与Rad60短暂结合。这种多蛋白复合物在维持染色体完整性和修复DNA双链断裂(DSB)中起重要作用。本研究对粟酒裂殖酵母突变体rad62 - 1进行了表征,该突变体对甲磺酸甲酯(MMS)敏感,并且与rad2合成致死(这是重组突变体的一个特征)。rad62 - 1对紫外线和γ射线敏感,与rhp51上位,并且在DSB修复方面存在缺陷。Rad62对细胞活力至关重要,并且在遗传上与rad60、smc6和brc1相互作用。Rad62蛋白与Smc5 - 6复合物物理结合。rad62 - 1与促进从停滞复制中恢复的基因(如rqh1、srs2和mus81)以及参与核苷酸切除修复的基因(如rad13和rad16)的突变体合成致死。这些结果表明,Rad62与Rad60一样,与Smc5 - 6复合物一起,在通过重组维持染色体完整性和从停滞复制中恢复方面起重要作用。