Conformational trapping of Mismatch Recognition Complex MSH2/MSH3 on repair-resistant DNA loops
Conformational trapping of Mismatch Recognition Complex MSH2/MSH3 on repair-resistant DNA loops
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DOI：
10.1073/pnas.1105461108
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发表时间：
2011-10-18
影响因子：
11.1
通讯作者：
McMurray, Cynthia T.
中科院分区：
文献类型：
--
作者：
Lang, Walter H.;Coats, Julie E.;McMurray, Cynthia T.
小异源双链环的插入和缺失是DNA中常见的突变，但为什么一些环易于突变而另一些环被有效修复尚不清楚。在这里，我们报告的错配识别复合物，MSH 2/MSH 3，区分修复能力和修复抗性环之间的感应其交界处的构象动力学。MSH 2/MSH 3结合、弯曲并从有修复能力的环解离以向下游修复发出信号。修复抗性胞嘧啶-腺嘌呤-鸟嘌呤（CAG）环采用独特的DNA连接，其捕获核苷酸结合的MSH 2/MSH 3，并抑制其从DNA解离。我们设想，连接动力学是一个积极的参与者和修复信号的构象调节器，并决定一个环是否被MSH 2/MSH 3删除或逃逸成为突变的前体。
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.