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酿酒酵母DNA复制的精确时空控制
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国家自然科学基金(31630005,31770084,31628011)


Spatiotemporal control of DNA replication in Saccharomyces cerevisiae
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    摘要:

    DNA复制是最基本的生命活动之一。DNA复制本身的错误及其过程控制的异常是细胞内基因组不稳定的主要来源,会导致细胞生长异常、衰老、癌变乃至死亡。为了保证基因组DNA能够精确且完整的复制,DNA复制受到严格的调控。在G1期,DNA复制解旋酶的核心组分Mcm2-7复合体被招募到复制起点,获得复制许可资格。进入S期后,在两个周期性蛋白激酶及多个支架蛋白的作用下,复制解旋酶的激活因子Cdc45和GINS复合体被招募至Mcm2-7,形成解旋酶全酶Cdc45-Mcm2-7-GINS (CMG)复合体。随后,众多复制相关蛋白在精准的时空控制下被招募至CMG平台并组装成复制机器,起始DNA双向复制。当相向而行的两个复制叉相遇,复制机器会从DNA链上解离下来,从而完成DNA复制。关于DNA复制过程的研究在近十年来取得了跨越式的突破。本文以酿酒酵母为例,围绕所有真核生物中都高度保守的DNA复制控制开关——CMG解旋酶,对真核生物DNA复制的最新进展进行综述。

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    DNA replication is one of the fundamental processes of all lives. Errors produced by DNA replication and abnormalities in its regulation are major sources of genomic instability in cells, leading to abnormal cell growth, aging, tumorigenesis and even death. In order to ensure accurate and complete duplication of genomic DNA, DNA replication is strictly regulated in all eukaryotes. In the G1 phase, the core component of the DNA replicative helicase——Mcm2-7 is recruited to the origins. This is called replication licensing. After cells entering the S phase, the helicase co-activators Cdc45 and GINS are recruited to Mcm2-7, forming the helicase holoenzyme Cdc45-Mcm2-7-GINS (CMG) complex. Subsequently, numerous replicating proteins are recruited to the CMG platform under precise spatiotemporal control and assembled into a replication machine to initiate bidirectional replication. When two converging replication forks encounter each other, CMGs are displaced to terminate the progression of these forks. The last decade has witnessed the leap-forward breakthroughs in this field, particularly in the model organism Saccharomyces cerevisiae. Here, we summarize the recent advances in eukaryotic DNA replication with a focus on the motor of replisome, DNA helicase CMG.

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刘路,楼慧强. 酿酒酵母DNA复制的精确时空控制[J]. 微生物学通报, 2019, 46(2): 354-361

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  • 在线发布日期: 2019-01-31
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