有丝分裂期DNA合成(MiDAS)及其介导的端粒复制  

Mitotic DNA Repair Synthesis and Its Mediated Telomere Replication

作　　者：余雨杨 侯凯龙 仝津恺 张艳多 贾舒婷 YU Yu-Yang;HOU Kai-Long;TONG Jin-Kai;ZHANG Yan-Duo;JIA Shu-Ting(Laboratory of Molecular Genetic of Aging&Tumor,Medical School,Kunming University of Science and Technology,Kunming 650500,China;Faculty of Life Science and Technology,Kunming University of Science and Technology,Kunming 650500,China)

机构地区：[1]昆明理工大学医学院衰老与肿瘤分子遗传学实验室,昆明650500 [2]昆明理工大学生命科学与技术学院,昆明650500

出　　处：《生物化学与生物物理进展》2022年第10期1918-1926,共9页Progress In Biochemistry and Biophysics

基　　金：云南省应用基础研究计划(2019FB109);云南省“万人计划”青年拔尖人才专项(YNWR-QNBJ-2019-240)资助项目。

摘　　要：DNA复制压力(replication stress,RS)是一个广泛定义DNA复制障碍的术语,通常是指那些能够扰乱复制进程,造成复制叉减慢或停滞的情况。复制压力的过度累积是肿瘤发生和基因组不稳定的主要驱动因素。细胞染色体在复制过程中会不断地遭受来自外源性或内源性复制压力,而端粒及常见脆性位点(common fragile sites,CFSs)是一类对复制压力高度敏感的区域,在复制压力较高的情况下,这些区域往往难以被完全复制。近年的研究发现,有丝分裂期DNA合成(mitotic DNA repair synthesis,MiDAS)区别于S期的复制,可以帮助难以复制的区域在进入有丝分裂期后仍然能够保证复制的进行,因此,MiDAS也被称为“复制的挽救机制”。由于端粒的维持依赖于端粒酶活性及端粒替代性延长机制(alternative lengthening of telomeres,ALT),而具有更多端粒脆性的ALT细胞中端粒-MiDAS表现出高度的活性,因此本文就MiDAS的发生机制及在不同端粒维持机制下难以复制的端粒如何应对复制压力在有丝分裂期完成DNA的合成进行综述。DNA replication stress(RS)is a term that broadly defines DNA replication disorders,and usually refers to events that cause replication forks to slow down or stall.The excessive accumulation of replication stress is the main driver of tumorigenesis and genome instability.Cell chromosomes constantly expose to exogenous or endogenous replication stress in replication,telomeres and common fragile sites are some chromosome regions that are highly sensitive to replication stress.These regions are usually difficult to completely replicate under high replication stress.Recent studies have found that mitotic DNA repair synthesis(MiDAS)is different from S phase replication,which can help difficult-to-replicate regions to be able to replicate after entering mitosis.Therefore,MiDAS is also called“rescue mechanism of replication”.Since the maintenance of telomeres depends on telomerase activity and alternative lengthening of telomeres(ALT),ALT cells have more fragility of telomeres,and MiDAS shows high levels of activity,so this reviews the mechanism of MiDAS and how difficult-to-replicate telomeres respond to replication stress to complete DNA synthesis during mitosis under different telomere maintenance mechanisms.

关 键 词：端粒复制 有丝分裂期DNA合成 复制压力 

分 类 号：Q71[生物学—分子生物学]