Kowalczykowski Stephen C
Department of Microbiology & Molecular Genetics and Department of Molecular and Cellular Biology, University of California, Davis, Davis, California 95616.
Cold Spring Harb Perspect Biol. 2015 Nov 2;7(11):a016410. doi: 10.1101/cshperspect.a016410.
Recombinational DNA repair is a universal aspect of DNA metabolism and is essential for genomic integrity. It is a template-directed process that uses a second chromosomal copy (sister, daughter, or homolog) to ensure proper repair of broken chromosomes. The key steps of recombination are conserved from phage through human, and an overview of those steps is provided in this review. The first step is resection by helicases and nucleases to produce single-stranded DNA (ssDNA) that defines the homologous locus. The ssDNA is a scaffold for assembly of the RecA/RAD51 filament, which promotes the homology search. On finding homology, the nucleoprotein filament catalyzes exchange of DNA strands to form a joint molecule. Recombination is controlled by regulating the fate of both RecA/RAD51 filaments and DNA pairing intermediates. Finally, intermediates that mature into Holliday structures are disjoined by either nucleolytic resolution or topological dissolution.
重组DNA修复是DNA代谢的一个普遍方面,对基因组完整性至关重要。它是一个模板导向的过程,利用第二条染色体拷贝(姐妹染色体、子代染色体或同源染色体)来确保断裂染色体的正确修复。重组的关键步骤从噬菌体到人类都是保守的,本文综述了这些步骤。第一步是通过解旋酶和核酸酶进行切除,以产生定义同源位点的单链DNA(ssDNA)。ssDNA是RecA/RAD51细丝组装的支架,促进同源性搜索。找到同源性后,核蛋白细丝催化DNA链交换形成连接分子。通过调节RecA/RAD51细丝和DNA配对中间体的命运来控制重组。最后,成熟为霍利迪结构的中间体通过核酸溶解或拓扑溶解而分离。