Coordinated protein and DNA conformational changes govern mismatch repair initiation by MutS.
Coordinated protein and DNA conformational changes govern mismatch repair initiation by MutS.
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DOI：
10.1093/nar/gky865
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发表时间：
2018-11-16
影响因子：
14.9
通讯作者：
Erie DA
中科院分区：
文献类型：
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作者：
LeBlanc SJ;Gauer JW;Hao P;Case BC;Hingorani MM;Weninger KR;Erie DA
MutS同源物识别复制过程中DNA中的碱基配对错误并启动修复。在三磷酸腺苷存在下，MutS诱导DNA在错配识别后弯曲，随后经历构象转变，促进其与MutL的相互作用以进行信号修复。在MutL不存在的情况下，这些转变导致形成MutS移动的钳，其可沿DNA沿着移动。以前的单分子FRET（smFRET）研究的特点MutS DNA结合结构域在这些过渡的动力学。在这里，我们使用蛋白质-DNA和DNA-DNA smFRET监测DNA构象变化，我们使用动力学分析，以相互关联的DNA和蛋白质的构象变化，并在路径上的步骤移动的钳形成。结果揭示了MutS和DNA中的多个连续结构变化，并且它们表明DNA动力学在MutS移动的钳的形成中起关键作用。将这些发现与我们之前研究的数据结合起来，我们提出了协调MutS和DNA构象变化的统一模型，其中错配修复的启动取决于DNA弯曲/伸直能量学和MutS构象变化与其核苷酸结合特性的平衡。
MutS homologs identify base-pairing errors made in DNA during replication and initiate their repair. In the presence of adenosine triphosphate, MutS induces DNA bending upon mismatch recognition and subsequently undergoes conformational transitions that promote its interaction with MutL to signal repair. In the absence of MutL, these transitions lead to formation of a MutS mobile clamp that can move along the DNA. Previous single-molecule FRET (smFRET) studies characterized the dynamics of MutS DNA-binding domains during these transitions. Here, we use protein–DNA and DNA–DNA smFRET to monitor DNA conformational changes, and we use kinetic analyses to correlate DNA and protein conformational changes to one another and to the steps on the pathway to mobile clamp formation. The results reveal multiple sequential structural changes in both MutS and DNA, and they suggest that DNA dynamics play a critical role in the formation of the MutS mobile clamp. Taking these findings together with data from our previous studies, we propose a unified model of coordinated MutS and DNA conformational changes wherein initiation of mismatch repair is governed by a balance of DNA bending/unbending energetics and MutS conformational changes coupled to its nucleotide binding properties.
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影响因子：
3
作者：
Brunger, Axel T.;Strop, Pavel;Vrljic, Marija;Chu, Steven;Weninger, Keith R.
通讯作者：
Weninger, Keith R.
影响因子：
64.5
作者：
FISHEL, R;LESCOE, MK;KOLODNER, R
通讯作者：
KOLODNER, R
影响因子：
64.5
作者：
Ban, C;Junop, M;Yang, W
通讯作者：
Yang, W
MUTS不匹配的DNA复合物的动力学可预测其修复表型。
影响因子：
2.9
作者：
DeRocco, Vanessa C.;Sass, Lauryn E.;Qiu, Ruoyi;Weninger, Keith R.;Erie, Dorothy A.
通讯作者：
Erie, Dorothy A.
影响因子：
16.8
作者：
通讯作者：
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