The unstructured linker arms of MutL enable GATC site incision beyond roadblocks during initiation of DNA mismatch repair
The unstructured linker arms of MutL enable GATC site incision beyond roadblocks during initiation of DNA mismatch repair
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MutL 的非结构化连接臂使 GATC 位点切口能够在 DNA 错配修复启动过程中超越障碍
DOI：
10.1101/463133
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发表时间：
2018
影响因子：
14.9
通讯作者：
J. Lebbink
中科院分区：
文献类型：
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作者：
Yannicka S N Mardenborough;Katerina Nitsenko;C. Laffeber;Camille Duboc;Enes Sahin;A. Quessada;H. Winterwerp;T. Sixma;R. Kanaar;P. Friedhoff;T. Strick;J. Lebbink
DNA错配修复（MMR）通过修复DNA复制错误来维持基因组的稳定性。在大肠杆菌中，MMR的起始涉及MutS识别错配、MutL募集、核酸内切酶MutH激活和DNA链在半甲基化GATC位点处切割。在这里，我们研究的通信机制，夫妇错配识别的子链切割。我们研究了催化缺陷型Cas9以及停滞的RNA聚合酶作为在整体和单分子纳米操纵切割测定中在错配和GATC位点之间放置在DNA上的路障的作用。观察到MMR蛋白切割GATC位点超过路障，尽管效率降低。在缩短MutL的无序接头区域后，该残余切口完全消除。这些结果表明，路障旁路可以完全归因于MutL中的长的、无序的接头区域，并确立了MMR起始期间的通信沿着DNA骨架发生。
DNA mismatch repair (MMR) maintains genome stability through repair of DNA replication errors. In Escherichia coli, initiation of MMR involves recognition of the mismatch by MutS, recruitment of MutL, activation of endonuclease MutH and DNA strand incision at a hemimethylated GATC site. Here we studied the mechanism of communication that couples mismatch recognition to daughter strand incision. We investigated the effect of catalytically-deficient Cas9 as well as stalled RNA polymerase as roadblocks placed on DNA in between the mismatch and GATC site in ensemble and single molecule nanomanipulation incision assays. The MMR proteins were observed to incise GATC sites beyond a roadblock, albeit with reduced efficiency. This residual incision is completely abolished upon shortening the disordered linker regions of MutL. These results indicate that roadblock bypass can be fully attributed to the long, disordered linker regions in MutL and establish that communication during MMR initiation occurs along the DNA backbone.
影响因子：
56.9
作者：
Jinek, Martin;Chylinski, Krzysztof;Charpentier, Emmanuelle
通讯作者：
Charpentier, Emmanuelle
影响因子：
64.8
作者：
通讯作者：
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DOI：
10.1073/pnas.1106696109
发表时间：
2012-02-07
影响因子：
11.1
作者：
Schoepf, Barbara;Bregenhorn, Stephanie;Jiricny, Josef
通讯作者：
Jiricny, Josef