MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity.
MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity.
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DOI：
10.1155/2014/574850
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Narayan G
中科院分区：
文献类型：
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作者：
Das M;Singh S;Pradhan S;Narayan G
微染色体维持（MCM）2-7复合物作为真核生物DNA复制解旋酶，是DNA复制许可系统的重要组成部分。六个相关的MCM蛋白形成异六聚体，并与ORC、CDC 6和Cdt 1结合形成复制前复合物。虽然MCM是众所周知的复制解旋酶，但它们在染色质上的过量和分布模式提出了一个悖论，称为“MCM悖论”。已经采取了几种方法来解决MCM悖论，并描述了多余的MCM分布在复制起点之外的目的。也有人提出了这些MCM的替代功能，而不是解旋酶。这篇评论的重点是几个模型和概念产生的MCM悖论，以解决他们的解旋酶功能相吻合，并提供了深入了解的概念，多余的MCMs是为了许可休眠的起源作为备份在复制压力。最后，我们扩展了我们对MCM水平变化的影响的看法。虽然正常细胞需要过量的MCM成分来承受压力，但必须在正常和恶性细胞中划定阈值水平。本文还对MCM生物学的研究前景进行了展望。
As a crucial component of DNA replication licensing system, minichromosome maintenance (MCM) 2–7 complex acts as the eukaryotic DNA replicative helicase. The six related MCM proteins form a heterohexamer and bind with ORC, CDC6, and Cdt1 to form the prereplication complex. Although the MCMs are well known as replicative helicases, their overabundance and distribution patterns on chromatin present a paradox called the “MCM paradox.” Several approaches had been taken to solve the MCM paradox and describe the purpose of excess MCMs distributed beyond the replication origins. Alternative functions of these MCMs rather than a helicase had also been proposed. This review focuses on several models and concepts generated to solve the MCM paradox coinciding with their helicase function and provides insight into the concept that excess MCMs are meant for licensing dormant origins as a backup during replication stress. Finally, we extend our view towards the effect of alteration of MCM level. Though an excess MCM constituent is needed for normal cells to withstand stress, there must be a delineation of the threshold level in normal and malignant cells. This review also outlooks the future prospects to better understand the MCM biology.