Saccharomyces cerevisiae MGS1 is essential in strains deficient in the RAD6-dependent DNA damage tolerance pathway
Saccharomyces cerevisiae MGS1 is essential in strains deficient in the RAD6-dependent DNA damage tolerance pathway
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DOI：
10.1093/emboj/21.8.2019
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发表时间：
2002-04-15
期刊：
影响因子：
11.4
通讯作者：
Shinagawa, H
中科院分区：
文献类型：
--
作者：
Hishida, T;Ohno, T;Shinagawa, H
酿酒酵母Mgs1蛋白具有DNA依赖性ATP酶和单链DNA退火活性，在维持基因组稳定性方面发挥重要作用。我们发现，mgs1是合成致死与rad6和表现出协同生长缺陷与rad18和rad5，这是成员的RAD6上位组的DNA复制过程中的DNA损伤的耐受性很重要。mgs1突变体对DNA损伤剂不敏感，但mgs1 rad5双突变体对羟基脲的敏感性增加，自发突变率大大增加。mgs1 rad18双突变体的生长缺陷受到SRS2中编码DNA解旋酶的突变或Rad52过表达的抑制。此外，mgs1突变抑制了编码DNA聚合酶δ的POL3突变体的温度敏感性。mgs1还抑制由大肠杆菌RuvC（一种细菌霍利迪连接解离酶）的表达引起的pol3突变体的生长缺陷。这些研究结果表明，MgS1是必不可少的，以防止基因组的不稳定性所造成的复制叉逮捕在细胞中缺乏的RAD6途径，并可能调节复制叉运动催化的酵母聚合酶δ。
Saccharomyces cerevisiae Mgs1 protein, which possesses DNA-dependent ATPase and single strand DNA annealing activities, plays a role in maintaining genomic stability. We found that mgs1 is synthetic lethal with rad6 and exhibits a synergistic growth defect with rad18 and rad5, which are members of the RAD6 epistasis group important for tolerance of DNA damage during DNA replication. The mgs1 mutant is not sensitive to DNA-damaging agents, but the mgs1 rad5 double mutant has increased sensitivity to hydroxyurea and a greatly increased spontaneous mutation rate. Growth defects of mgs1 rad18 double mutants are suppressed by a mutation in SRS2, encoding a DNA helicase, or by overexpression of Rad52. Moreover, mgs1 mutation suppresses the temperature sensitivity of mutants in POL3, encoding DNA polymerase delta. mgs1 also suppresses the growth defect of a pol3 mutant caused by expression of Escherichia coli RuvC, a bacterial Holliday junction resolvase. These findings suggest that Mgs1 is essential for preventing genome instability caused by replication fork arrest in cells deficient in the RAD6 pathway and may modulate replication fork movement catalyzed by yeast polymerase delta.