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Mind the replication gap
Royal Society Open Science ( IF 2.9 ) Pub Date : 2021-06-09 , DOI: 10.1098/rsos.201932
Camelia Mocanu 1 , Kok-Lung Chan 1
Affiliation  

Unlike bacteria, mammalian cells need to complete DNA replication before segregating their chromosomes for the maintenance of genome integrity. Thus, cells have evolved efficient pathways to restore stalled and/or collapsed replication forks during S-phase, and when necessary, also to delay cell cycle progression to ensure replication completion. However, strong evidence shows that cells can proceed to mitosis with incompletely replicated DNA when under mild replication stress (RS) conditions. Consequently, the incompletely replicated genomic gaps form, predominantly at common fragile site regions, where the converging fork-like DNA structures accumulate. These branched structures pose a severe threat to the faithful disjunction of chromosomes as they physically interlink the partially duplicated sister chromatids. In this review, we provide an overview discussing how cells respond and deal with the under-replicated DNA structures that escape from the S/G2 surveillance system. We also focus on recent research of a mitotic break-induced replication pathway (also known as mitotic DNA repair synthesis), which has been proposed to operate during prophase in an attempt to finish DNA synthesis at the under-replicated genomic regions. Finally, we discuss recent data on how mild RS may cause chromosome instability and mutations that accelerate cancer genome evolution.



中文翻译:

注意复制差距

与细菌不同,哺乳动物细胞在分离染色体以维持基因组完整性之前需要完成 DNA 复制。因此,细胞已经进化出有效的途径来恢复 S 期停滞和/或崩溃的复制叉,并在必要时延迟细胞周期进程以确保复制完成。然而,强有力的证据表明,在温和的复制应激 (RS) 条件下,细胞可以进行 DNA 不完全复制的有丝分裂。因此,不完全复制的基因组间隙形成,主要是在常见的脆弱位点区域,在那里聚合叉状 DNA 结构积累。这些分支结构对染色体的忠实分离构成了严重威胁,因为它们在物理上将部分复制的姐妹染色单体相互连接起来。在这次审查中,我们提供了一个概述,讨论细胞如何响应和处理从 S/G2 监视系统中逃脱的复制不足的 DNA 结构。我们还专注于最近对有丝分裂诱导复制途径(也称为有丝分裂 DNA 修复合成)的研究,该途径已被提议在前期运行,以尝试在复制不足的基因组区域完成 DNA 合成。最后,我们讨论了关于轻度 RS 如何导致染色体不稳定和突变加速癌症基因组进化的最新数据。它已被提议在前期操作,以尝试在复制不足的基因组区域完成 DNA 合成。最后,我们讨论了关于轻度 RS 如何导致染色体不稳定和突变加速癌症基因组进化的最新数据。它已被提议在前期操作,以尝试在复制不足的基因组区域完成 DNA 合成。最后,我们讨论了关于轻度 RS 如何导致染色体不稳定和突变加速癌症基因组进化的最新数据。

更新日期:2021-06-09
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