当前位置: X-MOL 学术Nat. Cell Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation
Nature Cell Biology ( IF 17.3 ) Pub Date : 2021-06-09 , DOI: 10.1038/s41556-021-00688-9
Yana van der Weegen 1 , Klaas de Lint 2 , Diana van den Heuvel 1 , Yuka Nakazawa 3, 4 , Tycho E T Mevissen 5 , Janne J M van Schie 2 , Marta San Martin Alonso 1, 6 , Daphne E C Boer 1 , Román González-Prieto 7 , Ishwarya V Narayanan 8 , Noud H M Klaassen 1 , Annelotte P Wondergem 1 , Khashayar Roohollahi 2 , Josephine C Dorsman 2 , Yuichiro Hara 3, 4 , Alfred C O Vertegaal 7 , Job de Lange 2 , Johannes C Walter 5 , Sylvie M Noordermeer 1, 6 , Mats Ljungman 8, 9 , Tomoo Ogi 3, 4 , Rob M F Wolthuis 2 , Martijn S Luijsterburg 1
Affiliation  

Cells employ transcription-coupled repair (TCR) to eliminate transcription-blocking DNA lesions. DNA damage-induced binding of the TCR-specific repair factor CSB to RNA polymerase II (RNAPII) triggers RNAPII ubiquitylation of a single lysine (K1268) by the CRL4CSA ubiquitin ligase. How CRL4CSA is specifically directed towards K1268 is unknown. Here, we identify ELOF1 as the missing link that facilitates RNAPII ubiquitylation, a key signal for the assembly of downstream repair factors. This function requires its constitutive interaction with RNAPII close to K1268, revealing ELOF1 as a specificity factor that binds and positions CRL4CSA for optimal RNAPII ubiquitylation. Drug–genetic interaction screening also revealed a CSB-independent pathway in which ELOF1 prevents R-loops in active genes and protects cells against DNA replication stress. Our study offers key insights into the molecular mechanisms of TCR and provides a genetic framework of the interplay between transcriptional stress responses and DNA replication.



中文翻译:

ELOF1 是一种转录偶联的 DNA 修复因子,可指导 RNA 聚合酶 II 泛素化

细胞采用转录偶联修复 (TCR) 来消除转录阻断 DNA 损伤。DNA 损伤诱导的 TCR 特异性修复因子 CSB 与 RNA 聚合酶 II (RNAPII) 的结合通过 CRL4 CSA泛素连接酶触发单个赖氨酸 (K1268) 的 RNAPII 泛素化。CRL4 CSA如何专门针对 K1268 尚不清楚。在这里,我们将 ELOF1 识别为促进 RNAPII 泛素化的缺失环节,这是组装下游修复因子的关键信号。此功能需要其与靠近 K1268 的 RNAPII 的本构相互作用,揭示 ELOF1 作为结合和定位 CRL4 CSA的特异性因子以获得最佳的 RNAPII 泛素化。药物-遗传相互作用筛选还揭示了一个 CSB 独立途径,其中 ELOF1 阻止活性基因中的 R 环并保护细胞免受 DNA 复制压力。我们的研究提供了对 TCR 分子机制的重要见解,并提供了转录应激反应和 DNA 复制之间相互作用的遗传框架。

更新日期:2021-06-09
down
wechat
bug