8b3g

Publication Abstract from PubMed

During transcription-coupled DNA repair (TCR), RNA polymerase II (Pol II) transitions from a transcriptionally active state to an arrested state that allows for removal of DNA lesions. This transition requires site-specific ubiquitylation of Pol II by the CRL4(CSA) ubiquitin ligase, a process that is facilitated by ELOF1 in an unknown way. Using cryogenic electron microscopy, biochemical assays and cell biology approaches, we found that ELOF1 serves as an adaptor to stably position UVSSA and CRL4(CSA) on arrested Pol II, leading to ligase neddylation and activation of Pol II ubiquitylation. In the presence of ELOF1, a transcription factor IIS (TFIIS)-like element in UVSSA gets ordered and extends through the Pol II pore, thus preventing reactivation of Pol II by TFIIS. Our results provide the structural basis for Pol II ubiquitylation and inactivation in TCR.

Structural basis for RNA polymerase II ubiquitylation and inactivation in transcription-coupled repair.,Kokic G, Yakoub G, van den Heuvel D, Wondergem AP, van der Meer PJ, van der Weegen Y, Chernev A, Fianu I, Fokkens TJ, Lorenz S, Urlaub H, Cramer P, Luijsterburg MS Nat Struct Mol Biol. 2024 Mar;31(3):536-547. doi: 10.1038/s41594-023-01207-0. , Epub 2024 Feb 5. PMID:38316879^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.