TY - JOUR
T1 - XPC–PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair
AU - Blessing, Charlotte
AU - Apelt, Katja
AU - van den Heuvel, Diana
AU - Gonzalez-Leal, Claudia
AU - Rother, Magdalena B.
AU - van der Woude, Melanie
AU - González-Prieto, Román
AU - Yifrach, Adi
AU - Parnas, Avital
AU - Shah, Rashmi G.
AU - Kuo, Tia Tyrsett
AU - Boer, Daphne E.C.
AU - Cai, Jin
AU - Kragten, Angela
AU - Kim, Hyun Suk
AU - Schärer, Orlando D.
AU - Vertegaal, Alfred C.O.
AU - Shah, Girish M.
AU - Adar, Sheera
AU - Lans, Hannes
AU - van Attikum, Haico
AU - Ladurner, Andreas G.
AU - Luijsterburg, Martijn S.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
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.
UR - https://www.scopus.com/pages/publications/85135805637
U2 - 10.1038/s41467-022-31820-4
DO - 10.1038/s41467-022-31820-4
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C2 - 35963869
AN - SCOPUS:85135805637
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4762
ER -