RNA聚合酶监视的DNA修复机制
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内蒙古大学生命科学学院,省部共建草原家畜生殖调控与繁育国家重点实验室,呼和浩特 010070

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国家自然科学基金(32060016) 和内蒙古大学本科一流课程建 设项目(21400-12105/014) 资助.


RNA Polymerase-surveilled Mechanisms for DNA Repair
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State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot 010070, China

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This work was supported by grants from The National Natural Science Foundation of China(32060016)and the Undergraduate First-class Course Construction Project of Inner Mongolia University(21400-12105/014)

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    摘要:

    生物体在正常生命过程中面临内/外因来源的DNA损伤,DNA损伤不仅影响基因正确复制,也阻碍其正常转录. 为避免DNA损伤带来的灾难性后果,生物体进化出一整套修复机制,以保证复制和转录的正确性、基因组的完整性和遗传的稳定性. 本文重点综述了RNA聚合酶监视(RNA polymerase-surveilled,RNAP-S)的DNA修复机制. 首先从RNA聚合酶(RNA polymerase,RNAP)的结构出发介绍了RNAP对DNA损伤的感知机制;其次讨论了滞留RNAP的回溯、与其模板DNA的解离以及后续修复机制的启动,真核细胞科凯恩综合征B蛋白(Cockayne syndrome protein B,CSB)及其泛素化和8-氧代鸟嘌呤DNA糖基化酶1(8-oxoguanine DNA glycosylase1,OGG1)介导的RNAP-S修复;最后探讨了RNAP-S损伤修复的生物学意义并展望其前景.

    Abstract:

    Living organisms are in threats of endogenous/exogenous DNA damages. DNA damage impedes both replication and transcription accuracy. To ensure correct replication and transcriptions, and subsequent genome integrity and genetic stability, living organisms have evolved different mechanisms for DNA repair. This review focused on RNA polymerase surveilled (RNAP-S) mechanisms for DNA repairs, and discussed biological significance of the RNAP-S repairs and perspectives. RNA polymerase (RNAP) structure is a complex, being composed of many subunits with different roles in RNAP function. RNAPII has a trigger loop (TL) and a bridge helix (BH), these domains sense DNA lesions during transcription. RNAP stalls at the DNA damage sites to avoid transcribing mutated mRNA, allowing the repair system to be recruited. Interestingly, Mfd and DksA dissociate the stalled RNAP while UvrD pulls back the stalled RNAP on the template DNA to expose the lesions for subsequent performance of lesion repairs. Similarly, the CSB protein, its ubiquitination and OGG1 mediate RNAP-S repairs in eukaryotic cells. Most recently, it has been shown that RNAPIII is involved in homologous recombination repair.

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王菲尔,杨绎煊,莫日根. RNA聚合酶监视的DNA修复机制[J].生物化学与生物物理进展,2021,48(11):1260-1272

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  • 收稿日期:2021-02-24
  • 最后修改日期:2021-04-07
  • 接受日期:2021-04-12
  • 在线发布日期: 2021-11-23
  • 出版日期: 2021-11-20