Blessing, CharlotteApelt, Katjavan den Heuvel, DianaGonzalez-Leal, ClaudiaRother, Magdalena Bvan der Woude, MelanieGonzález-Prieto, RománYifrach, AdiParnas, AvitalShah, Rashmi GKuo, Tia TyrsettBoer, Daphne E CCai, JinKragten, AngelaKim, Hyun-SukSchärer, Orlando DVertegaal, Alfred C OShah, Girish MAdar, SheeraLans, Hannesvan Attikum, HaicoLadurner, Andreas GLuijsterburg, Martijn S2023-05-032023-05-032022-08-13http://hdl.handle.net/10668/19540Cells 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/ChromatinDNADNA DamageDNA RepairDNA-Binding ProteinsPoly Adenosine Diphosphate RibosePoly(ADP-ribose) Polymerase Inhibitorsresearch article35963869open access10.1038/s41467-022-31820-42041-1723PMC9376112https://www.nature.com/articles/s41467-022-31820-4.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376112/pdf