Mismatch repair factor MSH2-MSH3 binds and alters the conformation of branched DNA structures predicted to form during genetic recombination
Mismatch repair factor MSH2-MSH3 binds and alters the conformation of branched DNA structures predicted to form during genetic recombination
复制标题
DOI：
10.1016/j.jmb.2006.05.032
复制
发表时间：
2006-07-14
影响因子：
5.6
通讯作者：
Alani, Eric
中科院分区：
文献类型：
--
作者：
Surtees, Jonnifer A.;Alani, Eric
酿酒酵母的遗传学研究预测，错配修复 (MMR) 因子 MSH2-MSH3 会结合并稳定单链退火和基因转换过程中形成的分支重组中间体。为了测试这个模型，我们构建了一系列预计在这些重组事件期间形成的 DNA 底物。我们在电泳迁移率变动测定中表明，酿酒酵母 MSH2-MSH3 特异性结合含有 3' 单链 DNA 的分支 DNA 底物，并且 ATP 刺激其从这些底物中释放。化学足迹分析表明，MSH2-MSH3 特异性结合在分支底物的双链/单链连接处，改变其构象并打开连接处。因此，MSH2-MSH3 与其底物结合产生了独特的核蛋白结构，该结构可能向下游修复步骤发出信号，包括与 MMR 和核仁切除修复因子的相互作用。 (c) 2006 Elsevier Ltd. 保留所有权利。
Genetic studies in Saccharomyces cerevisiae predict that the mismatch repair (MMR) factor MSH2-MSH3 binds and stabilizes branched recombination intermediates that form during single strand annealing and gene conversion. To test this model, we constructed a series of DNA substrates that are predicted to form during these recombination events. We show in an electrophoretic mobility shift assay that S. cerevisiae MSH2-MSH3 specifically binds branched DNA substrates containing 3' single-stranded DNA and that ATP stimulates its release from these substrates. Chemical footprinting analyses indicate that MSH2-MSH3 specifically binds at the double-strand/single-strand junction of branched substrates, alters its conformation and opens up the junction. Therefore, MSH2-MSH3 binding to its substrates creates a unique nucleoprotein structure that may signal downstream steps in repair that include interactions with MMR and nucleoticle excision repair factors. (c) 2006 Elsevier Ltd. All rights reserved.