调控 DNA 双链断裂修复途径选择：53BP1 的新焦点。
Regulation of DNA double-strand break repair pathway choice: a new focus on 53BP1.
机构信息
Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
出版信息
J Zhejiang Univ Sci B. 2021 Jan 15;22(1):38-46. doi: 10.1631/jzus.B2000306.
Abstract
Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break (DSB) signaling. P53-binding protein 1 (53BP1) plays a critical role in coordinating the DSB repair pathway choice and promotes the non-homologous end-joining (NHEJ)-mediated DSB repair pathway that rejoins DSB ends. New insights have been gained into a basic molecular mechanism that is involved in 53BP1 recruitment to the DNA lesion and how 53BP1 then recruits the DNA break-responsive effectors that promote NHEJ-mediated DSB repair while inhibiting homologous recombination (HR) signaling. This review focuses on the up- and downstream pathways of 53BP1 and how 53BP1 promotes NHEJ-mediated DSB repair, which in turn promotes the sensitivity of poly(ADP-ribose) polymerase inhibitor (PARPi) in BRCA1-deficient cancers and consequently provides an avenue for improving cancer therapy strategies.
摘要
维持细胞内稳态和基因组完整性是 DNA 双链断裂 (DSB) 信号转导的关键职责。p53 结合蛋白 1 (53BP1) 在协调 DSB 修复途径选择方面发挥着关键作用，并促进非同源末端连接 (NHEJ) 介导的 DSB 修复途径，使 DSB 末端重新连接。人们对涉及 53BP1 募集到 DNA 损伤部位的基本分子机制以及 53BP1 如何募集促进 NHEJ 介导的 DSB 修复的 DNA 断裂反应效应物的基本分子机制有了新的认识，同时抑制同源重组 (HR) 信号。本综述重点介绍了 53BP1 的上下游途径，以及 53BP1 如何促进 NHEJ 介导的 DSB 修复，这反过来又提高了 BRCA1 缺陷型癌症中聚 (ADP-核糖) 聚合酶抑制剂 (PARPi) 的敏感性，从而为改善癌症治疗策略提供了途径。
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