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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 细胞周期蛋白E在细胞复制前复合体（Pre-RC）的组装中起重要作用 从静止状态重新进入细胞周期。预RC的组装，其中涉及 六个MCM亚基（Mcm 2 -7）的负载是DNA复制的先决条件。我们发现 细胞周期蛋白E通过激活Cdk 2，促进Mcm 2加载到染色质上。此函数 部分通过促进Cdc 7信使RNA和蛋白质的积累介导， 然后磷酸化Mcm 2与此一致，Mcm 2的磷酸化模拟突变体 在Mcm 2负载方面可以绕过对Cdc 7的要求。此外，异位 Cdc 6和Cdc 7的表达可以挽救与 显性负性Cdk 2的表达。这些结果与细胞周期蛋白E的作用一致。 Cdk 2促进Cdc 6和Cdc 7的积累，这是Mcm 2负载所必需的 当细胞从静止状态重新进入细胞周期时。