Elf1 promotes Rad26's interaction with lesion-arrested Pol II for transcription-coupled repair.
Elf1 promotes Rad26's interaction with lesion-arrested Pol II for transcription-coupled repair.
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DOI：
10.1073/pnas.2314245121
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发表时间：
2024-01-16
影响因子：
11.1
通讯作者：
Leschziner, Andres E.
中科院分区：
文献类型：
--
作者：
Sarsam, Reta D.;Xu, Jun;Lahiri, Indrajit;Gong, Wenzhi;Li, Qingrong;Oh, Juntaek;Zhou, Zhen;Hou, Peini;Chong, Jenny;Hao, Nan;Lic, Shisheng;Wang, Dong;Leschziner, Andres E.
转录偶联核苷酸切除修复是一种保守的修复途径，其处理阻断转录的大体积病变。它需要核心转录偶联修复因子的协调来识别和区分损伤诱导的转录停滞与其他非损伤转录停滞。这项研究报告了几种不同的状态，转录偶联修复复合物，参与病变识别。我们还提出了结构-功能研究的病变逮捕Pol II复合物与两个基本的转录偶联修复因子-CSB/Rad 26和ERF 1/Elf 1-并揭示了它们之间的功能相互作用，在修复过程中，可能是保守的从酵母到人类。这项研究增强了我们对转录偶联修复的分子基础的认识。转录偶联核苷酸切除修复（TC-NER）是一种高度保守的DNA修复途径，可清除转录基因组中的大块病变。Cockayne综合征B蛋白（CS B）或其酵母直系同源物Rad 26，几十年来一直被认为在TC-NER的损伤识别步骤中发挥重要作用。另一个保守的蛋白ERF 1，或其酵母直系同源物Elf 1，最近被确定为核心转录偶联修复因子。Rad 26如何区分RNA聚合酶II（Pol II）停滞在DNA损伤或其他障碍物中，以及Elf 1在这一过程中扮演的角色仍然未知。在这里，我们展示了在不同障碍物处停滞的Pol II-Rad 26复合物的冷冻EM结构，这表明Rad 26使用共同的机制来识别停滞的Pol II，并且当Pol II在病变处停滞时会产生额外的相互作用。与Elf 1结合的病变被捕Pol II-Rad 26的冷冻电镜结构显示，Elf 1诱导Rad 26和病变被捕Pol II之间的进一步相互作用。生化和遗传数据支持Elf 1和Rad 26之间的相互作用在TC-NER启动的重要性。总之，我们的研究结果提供了重要的机制的见解，两个保守的转录偶联修复因子，Rad 26/CSB和Elf 1/CSF 1，在转录偶联修复的初始损伤识别步骤一起工作。
Transcription-coupled nucleotide excision repair is a conserved repair pathway that deals with bulky lesions that block transcription. It requires coordination of core transcription-coupled repair factors to recognize and distinguish lesion-induced transcription arrest from other non-lesion transcription arrest. This study reports several different states of transcription-coupled repair complexes that are involved in lesion recognition. We also present structure–function studies of lesion-arrested Pol II complexes with two essential transcription-coupled repair factors—CSB/Rad26 and ELOF1/Elf1—and reveal a functional interplay between them during repair that is likely conserved from yeast to human. This study enhances our knowledge of the molecular basis of transcription-coupled repair. Transcription-coupled nucleotide excision repair (TC-NER) is a highly conserved DNA repair pathway that removes bulky lesions in the transcribed genome. Cockayne syndrome B protein (CSB), or its yeast ortholog Rad26, has been known for decades to play important roles in the lesion-recognition steps of TC-NER. Another conserved protein ELOF1, or its yeast ortholog Elf1, was recently identified as a core transcription-coupled repair factor. How Rad26 distinguishes between RNA polymerase II (Pol II) stalled at a DNA lesion or other obstacles and what role Elf1 plays in this process remains unknown. Here, we present cryo-EM structures of Pol II-Rad26 complexes stalled at different obstacles that show that Rad26 uses a common mechanism to recognize a stalled Pol II, with additional interactions when Pol II is arrested at a lesion. A cryo-EM structure of lesion-arrested Pol II-Rad26 bound to Elf1 revealed that Elf1 induces further interactions between Rad26 and a lesion-arrested Pol II. Biochemical and genetic data support the importance of the interplay between Elf1 and Rad26 in TC-NER initiation. Together, our results provide important mechanistic insights into how two conserved transcription-coupled repair factors, Rad26/CSB and Elf1/ELOF1, work together at the initial lesion recognition steps of transcription-coupled repair.
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影响因子：
14.9
作者：
Li W;Giles C;Li S
通讯作者：
Li S
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
64.8
作者：
Kokic G;Wagner FR;Chernev A;Urlaub H;Cramer P
通讯作者：
Cramer P
影响因子：
2.6
作者：
GIETZ, RD;SCHIESTL, RH;WOODS, RA
通讯作者：
WOODS, RA
影响因子：
3.8
作者：
Li, Shisheng
通讯作者：
Li, Shisheng