MMS1-MMS22 COMPLEX PROTECTS GENOME INTEGRITY IN SCHIZOSACCHAROMYCES POMBE

MMS1-MMS22 复合物保护粟酒裂殖酵母基因组完整性

• 批准号: 8171474
• 负责人: PAUL RUSSELL
• 金额: $ 0.24万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171474
• 关键词: Camptothecin; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA Damage; DNA Repair; DNA Replication Damage; Data; Delayed Hypersensitivity; Exposure to; Fission Yeast; Funding; Genome; Grant; Growth; Holliday Junction Resolvases; Institution; Mitotic; Mutagens; Orthologous Gene; Phenotype; Proteins; Recovery; Reporting; Research; Research Personnel; Resources; Saccharomyces cerevisiae; Source; United States National Institutes of Health; base; homologous recombination; mutant; recombinational repair; ubiquitin-protein ligase

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mms1 and Mms22 are subunits of an Rtt101-based E3 ubiquitin ligase required for replication of damaged DNA templates in Saccharomyces cerevisiae. The function and evolutionary conservation of this DNA repair module are unknown. Here we report the characterization of an Mms1 ortholog in Schizosaccharomyces pombe. Fission yeast Mms1 was discovered through its physical association with S. pombe Mms22 (also known as Mus7). Loss of S. pombe Mms1 results in the accumulation of spontaneous DNA damage, mitotic delay, and hypersensitivity to genotoxins such as camptothecin that perturb replisome progression. Homologous recombination repair proteins Rhp51 and Rad22 (Rad51 and Rad52 orthologs, respectively) are critical for survival in the absence of Mms1; however, there is no such requirement for Mus81-Eme1 Holliday junction resolvase that is essential for recovery from broken replication forks. Mms1 and Mms22 mutants share similar phenotypes and are genetically epistatic under unperturbed growth conditions and following exposure to genotoxins. From these data we conclude that an evolutionary conserved Mms1-Mms22 complex is required for replication of damaged DNA in fission yeast.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 MMS1和MMS22是基于RTT101的E3泛素连接酶的亚基。 酿酒酵母中受损的DNA模板的复制。功能和 该DNA修复模块的进化保护尚不清楚。在这里，我们报告 schizosacchomyces pombe中MMS1直系同源物的表征。裂变酵母MMS1 通过与S. pombe MMS22（也称为MUS7）的物理关联发现。 S. pombe MMS1的损失导致自发DNA损伤的积累 延迟和对基因毒素（例如camptothecin）的超敏反应，使得扰动重壳体 进展。同源重组修复蛋白RHP51和RAD22（RAD51和RAD52 在没有MMS1的情况下，直系同源物对于生存至关重要。但是，没有 对MUS81-EME1 HOLLIDAY连接分辨率的这种要求对于恢复至关重要 从破碎的复制叉中。 MMS1和MMS22突变体具有相似的表型，并且是 在不受干扰的生长条件下以及暴露后的基因上位 基因毒素。从这些数据中，我们得出的结论是，进化保守的MMS1-MMS22 复制裂变酵母中受损的DNA需要复制。