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

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2022-08-13

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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

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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.

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Chromatin
DNA
DNA Damage
DNA Repair
DNA-Binding Proteins
Poly Adenosine Diphosphate Ribose
Poly(ADP-ribose) Polymerase Inhibitors

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