DNA双链断裂修复途径的选择与调控

Pathway choice for DNA double strand break repair

DNA双链断裂(double strand break, DSB)是一种导致基因组不稳定性的高毒性损伤,可引起染色质畸变诱发癌症.真核生物中演化出多条保守的DSB损伤修复途径,其中最重要的修复途径是典型的非同源末端连接(classical non-homologous end joining, cNHEJ)和同源重组(homologous recombination, HR),这两种修复途径解决了细胞中大多数的DSBs.对于不同类型的DSBs,细胞可以审时度势地选择最优的修复途径,以最低的基因组突变风险进行修复.依赖于不断发展的细胞成像技术和分子生物学方法,精细的DSB修复途径选择机制正逐渐展露出来,其调控机制十分复杂而且精密.本文主要阐述了断裂末端结构、DNA末端切除程度、细胞周期、染色质环境、组蛋白修饰和RNA代谢等因素对DSB修复途径的影响,展现了DSB修复途径选择的多样性和灵活性.

DNA double strand break(DSB) is a kind of highly toxic damage, causing genomic instability, chromatin aberration and cancer. A number of conserved DSB damage repair pathways have been found in eukaryotes, most notably classical non-homologous end joining(cNHEJ) and homologous recombination(HR). These two repair pathways resolve most DSBs in cells. For different types of DSBs, cells could wittily choose the optimal approach with the lowest risk for genomic instability. Relying on the developing cell imaging techniques and molecular biological methods, sophisticated mechanism of DSB repair pathway choice has been revealed.The regulation mechanism of pathway choice is complex and precise. In this review, the effect factors such as the structures of the broken terminals, the degree of DNA end resection, cell cycle, chromatin environment, histone modification and RNA metabolism on the DSB repair pathway choice are discussed, showing the diversity and flexibility of DSB repair pathway choice.