PHOSPH OF MCM2 BY CDC7 PROMOTES PRC ASSEMBLY DURING CELL-CYCLE RE-ENTRY

CDC7 对 MCM2 的磷酸化促进细胞周期重入期间的 PRC 组装

• 批准号: 8171473
• 负责人: Steven I Reed
• 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/8171473
• 关键词: Bypass; Cell Cycle; Cells; Chromatin; Computer Retrieval of Information on Scientific Projects Database; Cyclin E; DNA biosynthesis; Defect; Dominant-Negative Mutation; Ectopic Expression; Funding; Grant; Institution; Mediating; Messenger RNA; Pre-Replication Complex; Proteins; Research; Research Personnel; Resources; Role; Source; United States National Institutes of Health; mutant

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. Cyclin E has been shown to have a role in pre-replication complex (Pre-RC) assembly in cells re-entering the cell cycle from quiescence. The assembly of the pre-RC, which involves the loading of six MCM subunits (Mcm2-7), is a prerequisite for DNA replication. We found that cyclin E, through activation of Cdk2, promotes Mcm2 loading onto chromatin. This function is mediated in part by promoting the accumulation of Cdc7 messenger RNA and protein, which then phosphorylates Mcm2. Consistent with this, a phosphomimetic mutant of Mcm2 can bypass the requirement for Cdc7 in terms of Mcm2 loading. Furthermore, ectopic expression of both Cdc6 and Cdc7 can rescue the MCM loading defect associated with expression of dominant-negative Cdk2. These results are consistent with a role for cyclin E- Cdk2 in promoting the accumulation of Cdc6 and Cdc7, which is required for Mcm2 loading when cells re-enter the cell cycle from quiescence.

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。 细胞周期蛋白E已被证明在细胞中的复制复合物（PRE-RC）组装中起作用 从静止中重新进入细胞周期。 Pre-Rc的组装，涉及 六个MCM亚基（MCM2-7）的加载是DNA复制的先决条件。我们发现 通过激活CDK2，Cyclin E促进了MCM2载荷到染色质上。此功能 部分通过促进Cdc7 Messenger RNA和蛋白质的积累来介导 然后磷酸化MCM2。与此一致，MCM2的磷酸化突变体 可以根据MCM2加载绕过CDC7的需求。此外，异位 CDC6和CDC7的表达均可挽救与 显性阴性CDK2的表达。这些结果与细胞周期蛋白E-的作用一致 CDK2在促进CDC6和CDC7的积累中，这是MCM2加载所需的 当细胞从静止中重新进入细胞周期时。