CRISPR Publication Summary
ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation.
van der Weegen Y, de Lint K, van den Heuvel D, Nakazawa Y, Mevissen TET, van Schie JJM, San Martin Alonso M, Boer DEC, González-Prieto R, Narayanan IV, Klaassen NHM, Wondergem AP, Roohollahi K, Dorsman JC, Hara Y, Vertegaal ACO, de Lange J, Walter JC, Noordermeer SM, Ljungman M, Ogi T, Wolthuis RMF, Luijsterburg MS
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 CRL4 ubiquitin ligase. How CRL4 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 CRL4 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.
Nature cell biology | 2021-06-01 | PUBMED: 34108663
Supplementary Files:
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