Daley James M, Gaines William A, Kwon YoungHo, Sung Patrick
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06510.
Cold Spring Harb Perspect Biol. 2014 Sep 4;6(11):a017954. doi: 10.1101/cshperspect.a017954.
Homologous recombination (HR) is a major mechanism for eliminating DNA double-strand breaks from chromosomes. In this process, the break termini are resected nucleolytically to form 3' ssDNA (single-strand DNA) overhangs. A recombinase (i.e., a protein that catalyzes homologous DNA pairing and strand exchange) assembles onto the ssDNA and promotes pairing with a homologous duplex. DNA synthesis then initiates from the 3' end of the invading strand, and the extended DNA joint is resolved via one of several pathways to restore the integrity of the injured chromosome. It is crucial that HR be carefully orchestrated because spurious events can create cytotoxic intermediates or cause genomic rearrangements and loss of gene heterozygosity, which can lead to cell death or contribute to the development of cancer. In this review, we will discuss how DNA motor proteins regulate HR via a dynamic balance of the recombination-promoting and -attenuating activities that they possess.
同源重组（HR）是从染色体中消除DNA双链断裂的主要机制。在这个过程中，断裂末端通过核酸酶切除形成3'单链DNA（ssDNA）突出端。一种重组酶（即催化同源DNA配对和链交换的蛋白质）组装到ssDNA上，并促进与同源双链体的配对。然后从侵入链的3'端开始DNA合成，延伸的DNA接头通过几种途径之一进行解析，以恢复受损染色体的完整性。HR必须精心编排，这一点至关重要，因为错误事件会产生细胞毒性中间体，或导致基因组重排和基因杂合性丧失，进而导致细胞死亡或促进癌症的发展。在这篇综述中，我们将讨论DNA运动蛋白如何通过它们所具有的促进和减弱重组活性的动态平衡来调节HR。
