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An XPC-PARP axis links ALC1-mediated chromatin remodeling to global genome DNA damage repair

ABSTRACT: Cells employ global genome DNA damage 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-distorting DNA lesions, but binds inefficiently to lesions that cause poor helix distortion. How such 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. The close interaction between these proteins results in the PARylation of XPC at UV lesions, and an XPC-dependent stimulation of the poly-(ADP-ribose) response, which facilitates the recruitment of the poly-(ADP-ribose)-dependent chromatin remodeler ALC1. Both ALC1 and in particular PARP2 are required for the efficient clearing of difficult-to-repair DNA lesions. Our study offers key insights into the molecular mechanisms of GGR by revealing a molecular bookmarking system, which primes chromatin containing difficult-to-repair DNA lesions for efficient repair.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Román González-Prieto

LAB HEAD: Román González-Prieto

PROVIDER: PXD025226 | Pride | 2022-07-15

REPOSITORIES: Pride

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