Mimitou Eleni P, Symington Lorraine S
Department of Microbiology, Columbia University Medical Center, New York, NY 10032, USA.
Trends Biochem Sci. 2009 May;34(5):264-72. doi: 10.1016/j.tibs.2009.01.010. Epub 2009 Apr 15.
Homologous recombination (HR)-mediated DNA double-strand break repair maintains genome integrity. Although long-studied, an understanding of two essential steps in this process -- the resection of DNA ends to produce recombinogenic 3' single-stranded DNA tails and the resolution of recombination intermediates -- has remained elusive. Recent findings show an unexpected role for the Sgs1 (BLM) helicase and Dna2 nuclease in end resection, and provide mechanistic insight into the initiation of 5'-3' resection as well as its regulation by the cell cycle and the DNA damage response. Moreover, the identification of a novel Holliday junction resolvase, Yen1 (GEN1), and several helicases that dismantle strand invasion intermediates has increased the repertoire of nucleases and helicases capable of resolving recombination intermediates.
同源重组(HR)介导的DNA双链断裂修复维持基因组完整性。尽管对此进行了长期研究,但对这一过程中两个关键步骤——切除DNA末端以产生具有重组活性的3'单链DNA尾巴以及重组中间体的拆分——的理解仍然难以捉摸。最近的研究结果揭示了Sgs1(BLM)解旋酶和Dna2核酸酶在末端切除中的意外作用,并为5'-3'切除的起始及其受细胞周期和DNA损伤反应调控提供了机制上的见解。此外,一种新型Holliday连接体拆分酶Yen1(GEN1)以及几种拆解链侵入中间体的解旋酶的鉴定,增加了能够拆分重组中间体的核酸酶和解旋酶种类。