Published May 5, 2023
| Version v1
Publication
XPC–PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair
Contributors
Others:
- Universidad de Sevilla. Departamento de Biología Celular
- Deutsche Forschungsgemeinschaft / German Research Foundation (DFG)
- Dutch Cancer Society
- European Research Council (ERC)
- Netherlands Organization for Scientific Research
- Institute of Basic Science (IBS). Korea
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Israel Cancer Research Fund Research Career Development Award
- Israel Cancer Association
- Israel Science Foundation
- Dutch Research Council
- National Cancer Institute (USA)
Description
Cells employ global genome nucleotide excision repair (GGR) to eliminate a broad spectrum of DNA lesions, including those induced by UV light. The lesion-recognition factor XPC initiates repair of helix-destabilizing DNA lesions, but binds poorly to lesions such as CPDs that do not destabilize DNA. How difficult-to-repair lesions are detected in chromatin is unknown. Here, we identify the poly-(ADP-ribose) polymerases PARP1 and PARP2 as constitutive interactors of XPC. Their interaction results in the XPC-stimulated synthesis of poly-(ADP-ribose) (PAR) by PARP1 at UV lesions, which in turn enables the recruitment and activation of the PAR-regulated chromatin remodeler ALC1. PARP2, on the other hand, modulates the retention of ALC1 at DNA damage sites. Notably, ALC1 mediates chromatin expansion at UV-induced DNA lesions, leading to the timely clearing of CPD lesions. Thus, we reveal how chromatin containing difficult-to-repair DNA lesions is primed for repair, providing insight into mechanisms of chromatin plasticity during GGR.
Abstract
German Research Foundation 213249687 - SFB 1064, 325871075 - SFB 1309Abstract
Dutch Cancer Society KWF-YIG 11367Abstract
European Research Council 310913Abstract
Netherlands Organization for Scientific Research 711.018.007Abstract
Institute of Basic Science IBS-R022-A1Abstract
Natural Sciences and Engineering Research Council of Canada RGPIN-2016-05868, RGPAS-492875-2016Abstract
Israel Cancer Research Fund Research Career Development Award 3013004741Abstract
Dutch Research Council ENW-M (OCENW.KLEIN.090), ALW.016.161.320, VI.C.182.052Abstract
National Cancer Insitute P01- CA092584Abstract
Israel Cancer Association 20210078Abstract
Israel Science Foundation 1710/17Additional details
Identifiers
- URL
- https://idus.us.es/handle//11441/145506
- URN
- urn:oai:idus.us.es:11441/145506
Origin repository
- Origin repository
- USE