DNA Damage Response Laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms, London EN6 3LD, UK.
Nat Rev Mol Cell Biol. 2014 Jan;15(1):7-18. doi: 10.1038/nrm3719. Epub 2013 Dec 11.
DNA double-strand break (DSB) signalling and repair is crucial to preserve genomic integrity and maintain cellular homeostasis. p53-binding protein 1 (53BP1) is an important regulator of the cellular response to DSBs that promotes the end-joining of distal DNA ends, which is induced during V(D)J and class switch recombination as well as during the fusion of deprotected telomeres. New insights have been gained into the mechanisms underlying the recruitment of 53BP1 to damaged chromatin and how 53BP1 promotes non-homologous end-joining-mediated DSB repair while preventing homologous recombination. From these studies, a model is emerging in which 53BP1 recruitment requires the direct recognition of a DSB-specific histone code and its influence on pathway choice is mediated by mutual antagonism with breast cancer 1 (BRCA1).
DNA 双链断裂 (DSB) 的信号转导和修复对于维持基因组完整性和细胞内稳态至关重要。p53 结合蛋白 1 (53BP1) 是细胞对 DSB 反应的重要调节剂,它促进了末端 DNA 末端的连接,这在 V(D)J 和类别转换重组以及去保护端粒融合过程中被诱导。人们对 53BP1 募集到受损染色质的机制以及 53BP1 如何促进非同源末端连接介导的 DSB 修复,同时防止同源重组的机制有了新的认识。从这些研究中,出现了一种模型,其中 53BP1 的募集需要直接识别 DSB 特异性组蛋白密码,并且其对途径选择的影响是通过与乳腺癌 1 (BRCA1) 的相互拮抗来介导的。