RT Journal Article
T1 XPC-PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair.
A1 Blessing, Charlotte
A1 Apelt, Katja
A1 van den Heuvel, Diana
A1 Gonzalez-Leal, Claudia
A1 Rother, Magdalena B
A1 van der Woude, Melanie
A1 González-Prieto, Román
A1 Yifrach, Adi
A1 Parnas, Avital
A1 Shah, Rashmi G
A1 Kuo, Tia Tyrsett
A1 Boer, Daphne E C
A1 Cai, Jin
A1 Kragten, Angela
A1 Kim, Hyun-Suk
A1 Schärer, Orlando D
A1 Vertegaal, Alfred C O
A1 Shah, Girish M
A1 Adar, Sheera
A1 Lans, Hannes
A1 van Attikum, Haico
A1 Ladurner, Andreas G
A1 Luijsterburg, Martijn S
AB 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.
YR 2022
FD 2022-08-13
LK http://hdl.handle.net/10668/19540
UL http://hdl.handle.net/10668/19540
LA en
DS RISalud
RD Apr 6, 2025