Ranjha Lepakshi, Howard Sean M, Cejka Petr
Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
Department of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.
Chromosoma. 2018 Jun;127(2):187-214. doi: 10.1007/s00412-017-0658-1. Epub 2018 Jan 11.
DNA double-strand breaks arise accidentally upon exposure of DNA to radiation and chemicals or result from faulty DNA metabolic processes. DNA breaks can also be introduced in a programmed manner, such as during the maturation of the immune system, meiosis, or cancer chemo- or radiotherapy. Cells have developed a variety of repair pathways, which are fine-tuned to the specific needs of a cell. Accordingly, vegetative cells employ mechanisms that restore the integrity of broken DNA with the highest efficiency at the lowest cost of mutagenesis. In contrast, meiotic cells or developing lymphocytes exploit DNA breakage to generate diversity. Here, we review the main pathways of eukaryotic DNA double-strand break repair with the focus on homologous recombination and its various subpathways. We highlight the differences between homologous recombination and end-joining mechanisms including non-homologous end-joining and microhomology-mediated end-joining and offer insights into how these pathways are regulated. Finally, we introduce noncanonical functions of the recombination proteins, in particular during DNA replication stress.
DNA双链断裂在DNA暴露于辐射和化学物质时偶然产生，或源于有缺陷的DNA代谢过程。DNA断裂也可以通过程序性方式引入，比如在免疫系统成熟、减数分裂或癌症化疗或放疗期间。细胞已经发展出多种修复途径，这些途径会根据细胞的特定需求进行微调。因此，营养细胞采用的机制能够以最低的诱变成本，最高效地恢复断裂DNA的完整性。相比之下，减数分裂细胞或发育中的淋巴细胞利用DNA断裂来产生多样性。在这里，我们综述了真核生物DNA双链断裂修复的主要途径，重点关注同源重组及其各种子途径。我们强调了同源重组与末端连接机制（包括非同源末端连接和微同源性介导的末端连接）之间的差异，并深入探讨了这些途径是如何被调控的。最后，我们介绍了重组蛋白的非经典功能，特别是在DNA复制应激期间的功能。
