Phosphorylation of MCM4 by cdc2 protein kinase inhibits the activity of the minichromosome maintenance complex

被引:113
作者
Hendrickson, M
Madine, M
Dalton, S
Gautier, J
机构
[1] WELLCOME CRC INST,CAMBRIDGE CB2 1QR,ENGLAND
[2] COLUMBIA UNIV COLL PHYS & SURG,DEPT GENET & DEV,NEW YORK,NY 10032
[3] COLUMBIA UNIV COLL PHYS & SURG,DEPT DERMATOL,NEW YORK,NY 10032
基金
英国惠康基金;
关键词
DNA replication; cell cycle; protein kinases; Xenopus;
D O I
10.1073/pnas.93.22.12223
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In eukaryotes, tight regulatory mechanisms ensure the ordered progression through the cell cycle phases. The mechanisms that prevent chromosomal DNA replication from taking place more than once each cell cycle are thought to involve the function of proteins of the minichromosome maintenance (MCM) family, Here, pie demonstrate that Xenopus MCM4, a member of the MCM protein family related to Spcdc21/ScCDC54, is part of a large protein complex comprising several other MCM proteins. MCM4 undergoes cell cycle-dependent phosphorylation both in cleaving embryos and in cell-free extracts. MCM4 phosphorylation starts concomitantly with the clearing of the MCM complex from the chromatin during S phase. Phosphorylation is carried out by cdc2/cyclinB protein kinase, which phosphorylates MCM4 in vitro at identical sites as the ones phosphorylated in vivo. Phosphorylation is specific for cdc2 protein kinase since MCM4 is not a substrate for other members of the cdk family, Furthermore, phosphorylation of MCM4 dramatically reduces its affinity for the chromatin, We propose that the cell cycle-dependent phosphorylation of MCM4 is a mechanism which inactivates the MCM complex from late S phase through mitosis, thus preventing illegitimate DNA replication during that period of the cell cycle.
引用
收藏
页码:12223 / 12228
页数:6
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