RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex
RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex
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DOI：
10.1038/sj.emboj.7600684
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发表时间：
2005-06-01
期刊：
影响因子：
11.4
通讯作者：
Brown, GW
中科院分区：
文献类型：
--
作者：
Chang, M;Bellaoui, M;Brown, GW
SGS 1编码一种DNA解旋酶，其在人类细胞中的同源物包括BLM、WRN和RECQ 4基因，这些基因突变会导致癌症易感综合征。通过大规模遗传网络分析确定的合成遗传相互作用的聚类显示，基因RMI 1（RecQ介导的基因组不稳定性，也称为NCE 4和YPL 024 W）的遗传相互作用谱与SGS 1和TOP 3高度相似，表明Rmi 1和SGS 1/TOP 3复合体之间存在功能关系。我们表明Rmi 1与Sgs 1和Top3发生物理相互作用，并且是该复合体的第三个成员。缺乏RMI 1的细胞激活Rad 53检查点激酶，经历有丝分裂延迟，并显示重组修复蛋白Rad 52的重新定位增加，表明存在自发DNA损伤。与RMI 1在维持基因组完整性中的作用一致，rmi 1 Delta细胞表现出增加的重组频率和增加的总染色体重排频率。此外，Rmi 1 Delta菌株在暴露于DNA损伤剂时不能完全激活Rad 53，这表明Rmi 1也是Rad 53依赖性DNA损伤反应的重要组成部分。
SGS1 encodes a DNA helicase whose homologues in human cells include the BLM, WRN, and RECQ4 genes, mutations in which lead to cancer-predisposition syndromes. Clustering of synthetic genetic interactions identified by large-scale genetic network analysis revealed that the genetic interaction profile of the gene RMI1 ( RecQ-mediated genome instability, also known as NCE4 and YPL024W) was highly similar to that of SGS1 and TOP3, suggesting a functional relationship between Rmi1 and the Sgs1/Top3 complex. We show that Rmi1 physically interacts with Sgs1 and Top3 and is a third member of this complex. Cells lacking RMI1 activate the Rad53 checkpoint kinase, undergo a mitotic delay, and display increased relocalization of the recombination repair protein Rad52, indicating the presence of spontaneous DNA damage. Consistent with a role for RMI1 in maintaining genome integrity, rmi1 Delta cells exhibit increased recombination frequency and increased frequency of gross chromosomal rearrangements. In addition, rmi1 Delta strains fail to fully activate Rad53 upon exposure to DNA-damaging agents, suggesting that Rmi1 is also an important part of the Rad53-dependent DNA damage response.