DNA双链断裂修复过程中的重要蛋白53BP

53BP1: a Key Protei n in Repair of Double-Strand Breaks

DNA双链断裂(double-strand breaks,DSBs)修复对于保证基因组完整性以及维持细胞的平衡稳定性起着关键作用。p53结合蛋白1(p53-binding protein 1,53BP1)是针对产生的双链断裂损伤做出反应的重要调控因子。目前,研究人员对于53BP1被招募到受损的染色质上的过程,以及53BP1在DSBs修复过程中阻止同源重组(homologous recombination,HR)的同时推动非同源末端连接(non-homologous end-joining,NHEJ)的过程,已经有了新的认识。并且,近期的研究结果启发科学家们提出了一种新的模型,即53BP1的招募需要直接识别DSBs特异性的组蛋白密码,而53BP1发挥作用时的通路选择则与BRCA1蛋白的拮抗作用有关。结合近年来有关53BP1的研究进展,主要综述了53BP1的结构与功能特点,其作为调控因子在DSBs修复过程中发挥的作用,以及53BP1达到有效聚集的方式。

The repair of DNA double-strand breaks （DSBs） is crucial to preserve genomic integrity and maintain cellular homeostasis, p53-binding protein 1 （53BP1） is an important regulator in response to DSBs. So far, new insights have been gained into the mechanism underlying the recruitment of 53BP1 to damaged chromatin. Also, new evidences have been revealed how 53BP1 promotes non-homologous end-joining-mediated DSBs repair while preventing homologous recombination. In addition, based on recent studies, the new model has been put forward that 53BP1 recruitment requires the direct recognition of a DSBs-specific his- tone code and its pathway choice is mediated by mutual antagonism with BRCA1. Here, the structural and functional characteristics of 53BP1 are reviewed and an overview of its role as a mediator in DSBs repair pathway is presented, as well as its recruitment to damaged chromatin.