Mcm7, a subunit of the presumptive MCM helicase, modulates its own expression in conjunction with Mcm1
Mcm7, a subunit of the presumptive MCM helicase, modulates its own expression in conjunction with Mcm1
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DOI：
10.1074/jbc.m300699200
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发表时间：
2003-07-11
影响因子：
4.8
通讯作者：
Tye, BK
中科院分区：
文献类型：
--
作者：
Fitch, MJ;Donato, JJ;Tye, BK
酿酒酵母菌Mcm7蛋白是假定的异聚MCM解旋酶的一个亚基，它可以融化起源DNA并解绕复制叉。先前的研究表明，Mcm1组成性地结合MCM7启动子并调节MCM7的表达。在这里，我们发现Mcm7是Mcm1调控Mcm7表达的一个新的辅因子。MCM7 -1突变体中MCM7的转录增加，而Mcm1 -1突变体中MCM7的转录减少，这表明MCM7与Mcm1一起调节自身的表达。事实上，Mcm7刺激Mcm1与Mcm7启动子上游的早期细胞周期盒以及CDC6和MCM5结合。Mcm1结合这些启动子是组成性的，而Mcm7在M期晚期被募集，这与Mcm7在调节早期细胞周期基因的周期性表达中起直接作用是一致的。Mcm7在复制起始、复制延伸和自动调节中的多重作用与SV40病毒的大t抗原癌蛋白相似。
The Saccharomyces cerevisiae Mcm7 protein is a subunit of the presumed heteromeric MCM helicase that melts origin DNA and unwinds replication forks. Previous work showed that Mcm1 binds constitutively to the MCM7 promoter and regulates MCM7 expression. Here, we identify Mcm7 as a novel cofactor of Mcm1 in the regulation of MCM7 expression. Transcription of MCM7 is increased in the mcm7-1 mutant and decreased in the mcm1-1 mutant, suggesting that Mcm7 modulates its own expression in conjunction with Mcm1. Indeed, Mcm7 stimulates Mcm1 binding to the early cell cycle box upstream of the promoters of MCM7 as well as CDC6 and MCM5. Whereas Mcm1 binds these promoters constitutively, Mcm7 is recruited during late M phase, consistent with Mcm7 playing a direct role in modulating the periodic expression of early cell cycle genes. The multiple roles of Mcm7 in replication initiation, replication elongation, and autoregulation parallel those of the oncoprotein, the large T-antigen of the SV40 virus.