Phosphorylation of Mcm2 by Cdc7 Promotes Pre-replication Complex Assembly during Cell-Cycle Re-entry

被引：62

作者：

Chuang, Li-Chiou ^{[1
]}

Teixeira, Leonardo K. ^{[1
]}

Wohlschlegel, James A. ^{[1
,2
]}

Henze, Martha ^{[1
]}

Yates, John R. ^{[2
]}

Mendez, Juan ^{[3
]}

Reed, Steven I. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA

[3] Spanish Natl Canc Res Ctr CNIO, Mol Oncol Programme, DNA Replicat Grp, E-28029 Madrid, Spain

来源：

MOLECULAR CELL | 2009年 / 35卷 / 02期

基金：

美国国家卫生研究院;

关键词：

MINICHROMOSOME MAINTENANCE PROTEINS; EUKARYOTIC DNA-REPLICATION; S-PHASE; MAMMALIAN-CELLS; CDC7-RELATED KINASE; CDC7-DBF4; HELICASE; LOCALIZATION; INITIATION; ROLES;

D O I：

10.1016/j.molcel.2009.06.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：206 / 216

页数：11

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