DNA双链断裂（DSB）是细胞受到电离辐射后最严重的DNA损伤，导致细胞凋亡、细胞周期阻滞以及DNA损伤修复。DNA损伤发生后，激活细胞内DNA损伤应答，启动DSB修复通路同源重组（HR）和非同源重组末端连接（NHEJ）。HR修复分为联会前期、联会期和联会后期，以姐妹染色单体为模板，进行无错误修复，是保护基因组完整性的主要机制。对IR导致的DSB HR和NHEJ具有互补关系，G2和S期HR是主要修复方式。HR是肿瘤发病风险、预后指标和治疗靶点，合成致死是HR用于肿瘤靶向治疗的重要机制。本文主要对DSB修复过程中所涉及HR修复通路中的分子机制、合成致死概念及其与NHEJ修复的关系作一综述，并探讨其成为转化医学研究和潜在临床应用的可能性。%DNA double strand breakage (DSB) is the most significantly biological effect when cells are exposed to ionizing radiation (IR) which may result in apoptosis, checkpoint arrest, cellular senescence and DSB repair. DNA damage response (DDR) is activated with induction of DNA damage. The mechanisms involved in DSB repair include homologous recombination (HR) and non-homologous end-joining (NHEJ). HR, a template-dependent and mostly error-free pathway, plays a crucial role in protecting genome fidelity from DSB. It can be divided into three phases including presynaptic, synaptic and postsynaptic phases. For the repair of DSBs caused by IR, HR is mainly restricted in G2 and S phases while NHEJ and HR function complementarily. HR is related to the risk of tumorigenesis, predicts the survival of several kinds of carcinoma and is a novel target of cancer therapy. This article has comprehensively reviewed the progress in understanding of the mechanism of HR repair, its associated factors affecting the fidelity in DSB repair, the concept of synthetic lethality and its association with NHEJ repair. The potential of its clinical application by targeting specific DSB repair pathways is further explored.
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