Lyndaker Amy M, Alani Eric
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
Bioessays. 2009 Mar;31(3):315-21. doi: 10.1002/bies.200800195.
Eukaryotic genomes harbor a large number of homologous repeat sequences that are capable of recombining. Their potential to disrupt genome stability highlights the need to understand how homologous recombination processes are coordinated. The Saccharomyces cerevisiae Rad1-Rad10 endonuclease performs an essential role in recombination between repeated sequences, by processing 3' single-stranded intermediates formed during single-strand annealing and gene conversion events. Several recent studies have focused on factors involved in Rad1-Rad10-dependent removal of 3' nonhomologous tails during homologous recombination, including Msh2-Msh3, Slx4, and the newly identified Saw1 protein. Together, this new work provides a model for how Rad1-Rad10-dependent end processing is coordinated: Msh2-Msh3 stabilizes and prepares double-strand/single-strand junctions for Rad1-Rad10 cleavage, Saw1 recruits Rad1-Rad10 to 3' tails, and Slx4 mediates crosstalk between the DNA damage checkpoint machinery and Rad1-Rad10.
真核生物基因组含有大量能够发生重组的同源重复序列。它们破坏基因组稳定性的可能性凸显了理解同源重组过程如何协调的必要性。酿酒酵母Rad1-Rad10核酸内切酶在重复序列之间的重组中发挥着重要作用,通过处理单链退火和基因转换事件中形成的3'单链中间体来实现。最近的几项研究聚焦于同源重组过程中参与Rad1-Rad10依赖性去除3'非同源尾巴的因素,包括Msh2-Msh3、Slx4和新发现的Saw1蛋白。这项新研究共同提供了一个关于Rad1-Rad10依赖性末端加工如何协调的模型:Msh2-Msh3稳定双链/单链连接并为Rad1-Rad10切割做准备,Saw1将Rad1-Rad10招募到3'尾巴,而Slx4介导DNA损伤检查点机制与Rad1-Rad10之间的串扰。