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

Charlotte Blessing, Katja Apelt, Diana van den Heuvel, Claudia Gonzalez-Leal, Magdalena B. Rother, Melanie van der Woude, Román González-Prieto, Adi Yifrach, Avital Parnas, Rashmi G. Shah, Tia Tyrsett Kuo, Daphne E.C. Boer, Jin Cai, Angela Kragten, Hyun Suk Kim, Orlando D. Schärer, Alfred C.O. Vertegaal, Girish M. Shah, Sheera Adar, Hannes LansHaico van Attikum, Andreas G. Ladurner, Martijn S. Luijsterburg

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number4762
Number of pages18
JournalNature Communications
Issue number1
StatePublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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