Department of Life Sciences, Chung-Ang University, Seoul 156-756, Korea.
Mol Cell. 2013 Aug 22;51(4):440-53. doi: 10.1016/j.molcel.2013.08.008.
Recombinational repair of spontaneous double-strand breaks (DSBs) exhibits sister bias. DSB-initiated meiotic recombination exhibits homolog bias. Physical analysis in yeast reveals that, in both cases, the recombination reaction intrinsically gives homolog bias. From this baseline default, cohesin intervenes to confer sister bias, likely independent of cohesion. In meiosis, cohesin's sister-biasing effect is counteracted by RecA homolog Rad51 and its mediators, plus meiotic RecA homolog Dmc1, which thereby restore intrinsic homolog bias. Meiotic axis complex Red1/Mek1/Hop1 participates by cleanly switching recombination from mitotic to meiotic mode, concomitantly activating Dmc1. We propose that a Rad51/DNA filament at one DSB end captures the intact sister, creating an anchor pad. This filament extends across the DSB site on the intact partner, precluding intersister strand exchange, thus forcing use of the homolog. Cohesin and Dmc1 interactively modulate this extension, with program-appropriate effects. In accord with this model, Rad51-mediated recombination in vivo requires the presence of a sister.
自发双链断裂（DSBs）的重组修复表现出姐妹染色单体偏向性。DSB 引发的减数分裂重组表现出同源偏向性。酵母的物理分析表明，在这两种情况下，重组反应本质上都具有同源偏向性。从这个基本默认值出发，黏合蛋白通过独立于黏合作用来干预，从而赋予姐妹染色单体偏向性。在减数分裂中，黏合蛋白的姐妹染色单体偏向性效应被 RecA 同源物 Rad51 及其介导物以及减数分裂 RecA 同源物 Dmc1 抵消，从而恢复了内在的同源偏向性。减数分裂轴复合物 Red1/Mek1/Hop1 通过干净地将重组从有丝分裂切换到减数分裂模式来参与，同时激活 Dmc1。我们提出，一个位于一个 DSB 末端的 Rad51/DNA 丝在该 DSB 末端捕获完整的姐妹染色单体，形成一个锚定垫。该丝延伸穿过完整的供体上的 DSB 位点，排除姐妹染色单体间的链交换，从而迫使使用同源物。黏合蛋白和 Dmc1 相互作用地调节这种延伸，具有适当的程序效果。根据该模型，体内 Rad51 介导的重组需要存在一个姐妹染色单体。
