Transcription-coupled DNA-protein crosslink repair by CSB and CRL4CSA-mediated degradation.
Nat Cell Biol
; 26(5): 770-783, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38600236
ABSTRACT
DNA-protein crosslinks (DPCs) arise from enzymatic intermediates, metabolism or chemicals like chemotherapeutics. DPCs are highly cytotoxic as they impede DNA-based processes such as replication, which is counteracted through proteolysis-mediated DPC removal by spartan (SPRTN) or the proteasome. However, whether DPCs affect transcription and how transcription-blocking DPCs are repaired remains largely unknown. Here we show that DPCs severely impede RNA polymerase II-mediated transcription and are preferentially repaired in active genes by transcription-coupled DPC (TC-DPC) repair. TC-DPC repair is initiated by recruiting the transcription-coupled nucleotide excision repair (TC-NER) factors CSB and CSA to DPC-stalled RNA polymerase II. CSA and CSB are indispensable for TC-DPC repair; however, the downstream TC-NER factors UVSSA and XPA are not, a result indicative of a non-canonical TC-NER mechanism. TC-DPC repair functions independently of SPRTN but is mediated by the ubiquitin ligase CRL4CSA and the proteasome. Thus, DPCs in genes are preferentially repaired in a transcription-coupled manner to facilitate unperturbed transcription.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
RNA Polymerase II
/
DNA Helicases
/
DNA Repair Enzymes
/
DNA Repair
/
Proteolysis
/
Poly-ADP-Ribose Binding Proteins
Limits:
Humans
Language:
En
Journal:
Nat Cell Biol
Year:
2024
Document type:
Article
Affiliation country:
Netherlands