Cargando…

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

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....

Descripción completa

Detalles Bibliográficos
Autores principales: Blessing, Charlotte, Apelt, Katja, van den Heuvel, Diana, Gonzalez-Leal, Claudia, Rother, Magdalena B., van der Woude, Melanie, González-Prieto, Román, Yifrach, Adi, Parnas, Avital, Shah, Rashmi G., Kuo, Tia Tyrsett, Boer, Daphne E. C., Cai, Jin, Kragten, Angela, Kim, Hyun-Suk, Schärer, Orlando D., Vertegaal, Alfred C. O., Shah, Girish M., Adar, Sheera, Lans, Hannes, van Attikum, Haico, Ladurner, Andreas G., Luijsterburg, Martijn S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376112/
https://www.ncbi.nlm.nih.gov/pubmed/35963869
http://dx.doi.org/10.1038/s41467-022-31820-4
Descripción
Sumario: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.