生物学杂志

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跨损伤合成途径中真核生物DNA聚合酶δ转换机制的研究进展

  

  1. 江苏大学 生命科学研究院, 镇江 212013
  • 出版日期:2018-06-18 发布日期:2018-06-18
  • 通讯作者: 周亚竟,教授,主要从事DNA 复制、损伤与修复研究,E-mail:yajingzhou@ ujs. edu.cn
  • 作者简介:陈炜,硕士,主要从事DNA 损伤与修复研究,E-mail:chenweijsdx@ 163.com
  • 基金资助:
    国家自然科学基金(31370790)

Research progress on the mechanism of eukaryotic DNA polymerase δ switching in translesion synthesis

  1. Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, China
  • Online:2018-06-18 Published:2018-06-18

摘要: 为维护染色体结构的完整性和遗传稳定性,除了各种分工明确的损伤修复途径外,细胞还进化出一种跨损伤修复的损伤耐受机制,涉及一种被广为深入研究的有错跨损伤合成途径,即通过低保真跨损伤合成聚合酶临时取代复制聚合酶Pol δ,旁路通过受损碱基,使DNA损伤导致S-期暂停的复制叉进程得以恢复,这种复制聚合酶与跨损伤合成聚合酶之间的转换构成了有错跨损伤修复途径的核心,但对该途径聚合酶转换的激活机制存在争议。就真核生物DNA聚合酶δ的结构和功能以及在跨损伤合成途径聚合酶转换的激活机制等方面进行综述。

关键词: DNA聚合酶Pol &delta, ;跨损伤合成聚合酶;增殖细胞核抗原;泛素化修饰;聚合酶转换机制

Abstract: In order to maintain the integrity of chromosomal structure and genetic stability, in addition to those elaborate DNA damage repair mechanisms to remove DNA lesions, cells have also evolved DNA damage tolerance mechanisms to bypass damage. One extensively studied lesion-bypass pathway is translesion synthesis(TLS), an error-prone repair pathway, in which replicative polymerase δ is replaced with a specialized TLS polymerase, a low fidelity enzyme, which is able to by-pass lesions, allowing stalled replication fork in S-phase to proceed. The switching between replicative and TLS polymerases is generally considered to be a core in TLS pathway. However, there remains much controversy on the exact mechanism of polymerase switching. This article briefly reviewed and discussed researches about biological properties of eukaryotic DNA polymerase δ, structure and function of its subunits, and activation mechanisms of polymerase switching in TLS pathway, etc.

Key words: DNA polymerase Pol δ, TLS polymerase, proliferating cell nuclear antigen(PCNA), ubiquitin modification, polymerase switching mechanism