XPC-PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair

Blessing, Charlotte; Apelt, Katja; Heuvel, Diana van den; Gonzalez-Leal, Claudia; Rother, Magdalena B.; Woude, Melanie van der; Gonzalez-Prieto, Roman; Yifrach, Adi; Parnas, Avital; Shah, Rashmi G.; Kuo, Tia Tyrsett; Boer, Daphne E. C.; Cai, Jin; Kragten, Angela; Kim, Hyun-Suk; Scharer, Orlando D.; Vertegaal, Alfred C. O.; Shah, Girish M.; Adar, Sheera; Lans, Hannes; Attikum, Haico van; Ladurner, Andreas G. und Luijsterburg, Martijn S. (2022): XPC-PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair. In: Nature Communications, Bd. 13, Nr. 1, 4762

Abstract

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. Cells employ global genome nucleotide excision repair to repair a broad spectrum of genomic DNA lesions. Here, the authors reveal how chromatin is primed for repair, providing insight into mechanisms of chromatin plasticity during DNA repair.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 213249687
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 325871075