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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 细胞周期蛋白 E 已被证明在细胞中的复制前复合物 (Pre-RC) 组装中发挥作用 从静止期重新进入细胞周期。预RC的组装，其中涉及 六个 MCM 亚基 (Mcm2-7) 的加载是 DNA 复制的先决条件。我们发现 cyclin E 通过激活 Cdk2，促进 Mcm2 装载到染色质上。这个功能 部分是通过促进 Cdc7 信使 RNA 和蛋白质的积累来介导的， 然后磷酸化 Mcm2。与此一致的是，Mcm2 的拟磷突变体 可以绕过 Cdc7 在 Mcm2 负载方面的要求。此外，异位 Cdc6 和 Cdc7 的表达可以挽救与 显性失活 Cdk2 的表达。这些结果与细胞周期蛋白 E 的作用一致 Cdk2促进Cdc6和Cdc7的积累，这是Mcm2加载所必需的 当细胞从静止状态重新进入细胞周期时。