Publication of IMPRS-LS student Charlotte Blessing

Blessing, C., Apelt, K., van den Heuvel, D., Gonzalez-Leal, C., Rother, M.B., van der Woude, M., González-Prieto, R., Yifrach, A., Parnas, A., Shah, R.G., Kuo, T.T., Boer, D.E.C., Cai, J., Kragten, A., Kim, H.S., Schärer, O.D., Vertegaal, A.C.O., Shah, G.M., Adar, S., Lans, H., van Attikum, H., Ladurner, A.G., and Luijsterburg, M.S.
(IMPRS-LS students are in bold)
Nat Commun, 2022, 13, 4762.
doi: 10.1038/s41467-022-31820-4

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

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.