Ceccaldi Raphael, Rondinelli Beatrice, D'Andrea Alan D
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Trends Cell Biol. 2016 Jan;26(1):52-64. doi: 10.1016/j.tcb.2015.07.009. Epub 2015 Oct 1.
DNA double-strand breaks (DSBs) are cytotoxic lesions that threaten genomic integrity. Failure to repair a DSB has deleterious consequences, including genomic instability and cell death. Indeed, misrepair of DSBs can lead to inappropriate end-joining events, which commonly underlie oncogenic transformation due to chromosomal translocations. Typically, cells employ two main mechanisms to repair DSBs: homologous recombination (HR) and classical nonhomologous end joining (C-NHEJ). In addition, alternative error-prone DSB repair pathways, namely alternative end joining (alt-EJ) and single-strand annealing (SSA), have been recently shown to operate in many different conditions and to contribute to genome rearrangements and oncogenic transformation. Here, we review the mechanisms regulating DSB repair pathway choice, together with the potential interconnections between HR and the annealing-dependent error-prone DSB repair pathways.
DNA双链断裂（DSB）是一种细胞毒性损伤，会威胁基因组的完整性。未能修复DSB会产生有害后果，包括基因组不稳定和细胞死亡。事实上，DSB的错误修复会导致不适当的末端连接事件，这通常是由于染色体易位导致致癌转化的基础。通常，细胞采用两种主要机制来修复DSB：同源重组（HR）和经典非同源末端连接（C-NHEJ）。此外，最近研究表明，替代的易出错DSB修复途径，即替代末端连接（alt-EJ）和单链退火（SSA），在许多不同条件下起作用，并导致基因组重排和致癌转化。在这里，我们综述了调节DSB修复途径选择的机制，以及HR与依赖退火的易出错DSB修复途径之间的潜在联系。
