| Literature DB >> 34108663 |
Yana van der Weegen1, Klaas de Lint2, Diana van den Heuvel1, Yuka Nakazawa3,4, Tycho E T Mevissen5, Janne J M van Schie2, Marta San Martin Alonso1,6, Daphne E C Boer1, Román González-Prieto7, Ishwarya V Narayanan8, Noud H M Klaassen1, Annelotte P Wondergem1, Khashayar Roohollahi2, Josephine C Dorsman2, Yuichiro Hara3,4, Alfred C O Vertegaal7, Job de Lange2, Johannes C Walter5, Sylvie M Noordermeer1,6, Mats Ljungman8,9, Tomoo Ogi3,4, Rob M F Wolthuis10, Martijn S Luijsterburg11.
Abstract
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.Entities:
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Year: 2021 PMID： 34108663 PMCID： PMC8890769 DOI： 10.1038/s41556-021-00688-9
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.213