修复抗性 DNA 环上错配识别复合物 MSH2/MSH3 的构象捕获。
Conformational trapping of mismatch recognition complex MSH2/MSH3 on repair-resistant DNA loops.
机构信息
Lawrence Berkeley National Laboratory, Life Sciences Division, 1 Cyclotron Road, Berkeley, CA 94720, USA.
出版信息
Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):E837-44. doi: 10.1073/pnas.1105461108. Epub 2011 Sep 29.
Abstract
Insertion and deletion of small heteroduplex loops are common mutations in DNA, but why some loops are prone to mutation and others are efficiently repaired is unknown. Here we report that the mismatch recognition complex, MSH2/MSH3, discriminates between a repair-competent and a repair-resistant loop by sensing the conformational dynamics of their junctions. MSH2/MSH3 binds, bends, and dissociates from repair-competent loops to signal downstream repair. Repair-resistant Cytosine-Adenine-Guanine (CAG) loops adopt a unique DNA junction that traps nucleotide-bound MSH2/MSH3, and inhibits its dissociation from the DNA. We envision that junction dynamics is an active participant and a conformational regulator of repair signaling, and governs whether a loop is removed by MSH2/MSH3 or escapes to become a precursor for mutation.
摘要
小异源双链环的插入和缺失是 DNA 中的常见突变，但为什么有些环容易发生突变，而有些则能有效地修复，目前尚不清楚。在这里，我们报告说，错配识别复合物 MSH2/MSH3 通过感知其连接点的构象动力学，区分修复有能力的环和修复抗性环。MSH2/MSH3 结合、弯曲和解离修复有能力的环，以发出下游修复信号。修复抗性胞嘧啶-腺嘌呤-鸟嘌呤（CAG）环采用一种独特的 DNA 连接点，捕获核苷酸结合的 MSH2/MSH3，并抑制其从 DNA 上解离。我们设想连接点动力学是修复信号传导的积极参与者和构象调节剂，并控制环是否被 MSH2/MSH3 去除，还是逃脱成为突变的前体。
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