Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair.
Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair.
复制标题
DOI：
10.1038/s41467-021-27295-4
复制
发表时间：
2021-12-01
影响因子：
16.6
通讯作者：
Ivanov I
中科院分区：
文献类型：
--
作者：
Yan C;Dodd T;Yu J;Leung B;Xu J;Oh J;Wang D;Ivanov I
转录偶联修复对于从转录的基因组中去除DNA损伤是必不可少的。该途径由CSB蛋白与停滞的RNA聚合酶II结合启动。损害CSB功能的突变会导致严重的遗传疾病。然而，CSB使RNA聚合酶绕过某些病变而触发切除其他病变的ATP依赖性机制尚不完全清楚。在这里，我们建立了RNA聚合酶II在无核苷酸和结合状态下与酵母CSB直系同源物Rad 26结合的结构模型。这使得模拟和图论分析能够定义将该复合物划分为动态社区，并描绘其结构元素如何一起作用以重塑DNA。我们确定了一个变构途径耦合Rad 26 ATP酶模块的运动，RNA聚合酶和DNA的变化，揭示了一个结构机制，为CSB辅助的进展过去体积较小的病变。我们的模型允许对Cockayne综合征疾病突变的影响进行功能解释。在本文中，作者提供了RNA聚合酶II与不同核苷酸状态的酵母CSB直系同源物Rad 26结合的模型;解释了Rad 26结构域运动如何帮助聚合酶通过DNA损伤;并解释了CSB相关疾病突变的影响。
Transcription-coupled repair is essential for the removal of DNA lesions from the transcribed genome. The pathway is initiated by CSB protein binding to stalled RNA polymerase II. Mutations impairing CSB function cause severe genetic disease. Yet, the ATP-dependent mechanism by which CSB powers RNA polymerase to bypass certain lesions while triggering excision of others is incompletely understood. Here we build structural models of RNA polymerase II bound to the yeast CSB ortholog Rad26 in nucleotide-free and bound states. This enables simulations and graph-theoretical analyses to define partitioning of this complex into dynamic communities and delineate how its structural elements function together to remodel DNA. We identify an allosteric pathway coupling motions of the Rad26 ATPase modules to changes in RNA polymerase and DNA to unveil a structural mechanism for CSB-assisted progression past less bulky lesions. Our models allow functional interpretation of the effects of Cockayne syndrome disease mutations. Here the authors provide models of RNA polymerase II bound to the yeast CSB ortholog Rad26 in different nucleotide states; explain how Rad26 domain motions help the polymerase progress past DNA lesions; and interpret the effects of CSB-associated disease mutations.
登录
查看更多内容
影响因子：
16
作者：
Lake, Robert J.;Geyko, Anastasia;Fan, Hua-Ying
通讯作者：
Fan, Hua-Ying
影响因子：
4.8
作者：
Citterio, E;Rademakers, S;Vermeulen, W
通讯作者：
Vermeulen, W
DOI：
10.1107/s2059798318009324
发表时间：
2018-09-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Afonine PV;Klaholz BP;Moriarty NW;Poon BK;Sobolev OV;Terwilliger TC;Adams PD;Urzhumtsev A
通讯作者：
Urzhumtsev A
影响因子：
16
作者：
Anindya R;Mari PO;Kristensen U;Kool H;Giglia-Mari G;Mullenders LH;Fousteri M;Vermeulen W;Egly JM;Svejstrup JQ
通讯作者：
Svejstrup JQ
影响因子：
56.9
作者：
Brueckner, Florian;Hennecke, Ulrich;Cramer, Patrick
通讯作者：
Cramer, Patrick