Schizosaccharomyces pombe Minichromosome Maintenance-binding Protein (MCM-BP) Antagonizes MCM Helicase
Schizosaccharomyces pombe Minichromosome Maintenance-binding Protein (MCM-BP) Antagonizes MCM Helicase
复制标题
DOI：
10.1074/jbc.m111.282541
复制
发表时间：
2011-09-23
影响因子：
4.8
通讯作者：
Forsburg, Susan L.
中科院分区：
文献类型：
--
作者：
Ding, Lin;Forsburg, Susan L.
微染色体维持复合物（MCM）是一种复制性解旋酶，是DNA复制和基因组稳定性所必需的异源六聚体。我们鉴定了粟酒裂殖酵母mcb 1（+）（Mcm结合蛋白1），一种与MCM复合蛋白亚组相关的人MCM结合蛋白的明显直系同源物。McB 1（+）是一个必需基因。mcb 1（+）的缺失导致cdc表型细胞数代后细胞周期停滞，并破坏核结构。Mcb 1是一种丰富的蛋白质，组成性地存在于整个细胞周期中。它广泛分布于细胞质和核质中，并与染色质结合。免疫共沉淀表明Mcb 1与Mcm 3 -7强烈相互作用，但不与Mcm 2相互作用。Mcb 1的过量产生破坏了Mcm 2与其他MCM蛋白的结合，导致DNA复制抑制、DNA损伤和检查点激酶Chk 1的激活。因此，Mcb 1似乎拮抗MCM解旋酶的功能。
The minichromosome maintenance (MCM) complex, a replicative helicase, is a heterohexamer essential for DNA duplication and genome stability. We identified Schizosaccharomyces pombe mcb1(+) (Mcm-binding protein 1), an apparent orthologue of the human MCM-binding protein that associates with a subset of MCM complex proteins. mcb1(+) is an essential gene. Deletion of mcb1(+) caused cell cycle arrest after several generations with a cdc phenotype and disrupted nuclear structure. Mcb1 is an abundant protein, constitutively present across the cell cycle. It is widely distributed in cytoplasm and nucleoplasm and bound to chromatin. Co-immunoprecipitation suggested that Mcb1 interacts robustly with Mcm3-7 but not Mcm2. Overproduction of Mcb1 disrupted the association of Mcm2 with other MCM proteins, resulting in inhibition of DNA replication, DNA damage, and activation of the checkpoint kinase Chk1. Thus, Mcb1 appears to antagonize the function of MCM helicase.