ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation.
Nat Cell Biol
; 23(6): 595-607, 2021 06.
Article
in En
| MEDLINE
| ID: mdl-34108663
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA Damage
/
RNA Polymerase II
/
Peptide Elongation Factor 1
/
Ubiquitin-Protein Ligases
/
DNA Repair
/
Ubiquitination
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Cell Biol
Year:
2021
Document type:
Article
Affiliation country:
Netherlands
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM