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Sgs1在DNA复制中间体修复中的功能与其在同源重组修复中的作用是可分离的。

Sgs1 function in the repair of DNA replication intermediates is separable from its role in homologous recombinational repair.

作者信息

Bernstein Kara A, Shor Erika, Sunjevaric Ivana, Fumasoni Marco, Burgess Rebecca C, Foiani Marco, Branzei Dana, Rothstein Rodney

机构信息

Department of Genetics & Development, Columbia University Medical Center, New York, NY 10032, USA.

出版信息

EMBO J. 2009 Apr 8;28(7):915-25. doi: 10.1038/emboj.2009.28. Epub 2009 Feb 12.

Abstract

Mutations in human homologues of the bacterial RecQ helicase cause diseases leading to cancer predisposition and/or shortened lifespan (Werner, Bloom, and Rothmund-Thomson syndromes). The budding yeast Saccharomyces cerevisiae has one RecQ helicase, Sgs1, which functions with Top3 and Rmi1 in DNA repair. Here, we report separation-of-function alleles of SGS1 that suppress the slow growth of top3Delta and rmi1Delta cells similar to an SGS1 deletion, but are resistant to DNA damage similar to wild-type SGS1. In one allele, the second acidic region is deleted, and in the other, only a single aspartic acid residue 664 is deleted. sgs1-D664Delta, unlike sgs1Delta, neither disrupts DNA recombination nor has synthetic growth defects when combined with DNA repair mutants. However, during S phase, it accumulates replication-associated X-shaped structures at damaged replication forks. Furthermore, fluorescent microscopy reveals that the sgs1-D664Delta allele exhibits increased spontaneous RPA foci, suggesting that the persistent X-structures may contain single-stranded DNA. Taken together, these results suggest that the Sgs1 function in repair of DNA replication intermediates can be uncoupled from its role in homologous recombinational repair.

摘要

细菌RecQ解旋酶的人类同源物发生突变会导致疾病,引发癌症易感性和/或缩短寿命(沃纳综合征、布卢姆综合征和罗思蒙德-汤姆森综合征)。芽殖酵母酿酒酵母有一个RecQ解旋酶Sgs1,它在DNA修复中与Top3和Rmi1共同发挥作用。在此,我们报告了SGS1的功能分离等位基因,这些等位基因抑制top3Δ和rmi1Δ细胞的缓慢生长,类似于SGS1缺失,但对DNA损伤具有抗性,类似于野生型SGS1。在一个等位基因中,第二个酸性区域被删除,在另一个等位基因中,仅单个天冬氨酸残基664被删除。与sgs1Δ不同,sgs1-D664Δ既不破坏DNA重组,与DNA修复突变体结合时也没有合成生长缺陷。然而,在S期,它在受损的复制叉处积累与复制相关的X形结构。此外,荧光显微镜检查显示,sgs1-D664Δ等位基因表现出自发RPA病灶增加,这表明持续的X结构可能含有单链DNA。综上所述,这些结果表明,Sgs1在DNA复制中间体修复中的功能可以与其在同源重组修复中的作用分离。

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