Chromatin remodeler CHD 1 promotes XPC ‐to‐ TFIIH handover of nucleosomal UV lesions in nucleotide excision repair

Abstract

Ultraviolet ( UV ) light induces mutagenic cyclobutane pyrimidine dimers ( CPD s) in nucleosomal DNA that is tightly wrapped around histone octamers. How global‐genome nucleotide excision repair ( GG ‐ NER ) processes CPD s despite that this chromatin arrangement is poorly understood. An increased chromatin association of CHD 1 (chromodomain helicase DNA ‐binding 1) upon UV irradiation indicated possible roles of this chromatin remodeler in the UV damage response. Immunoprecipitation of chromatin fragments revealed that CHD 1 co‐localizes in part with GG ‐ NER factors. Chromatin fractionation showed that the UV ‐dependent recruitment of CHD 1 occurs to UV lesions in histone‐assembled nucleosomal DNA and that this CHD 1 relocation requires the lesion sensor XPC (xeroderma pigmentosum group C). In situ immunofluorescence analyses further demonstrate that CHD 1 facilitates substrate handover from XPC to the downstream TFIIH (transcription factor IIH ). Consequently, CHD 1 depletion slows down CPD excision and sensitizes cells to UV ‐induced cytotoxicity. The finding of a CHD 1‐driven lesion handover between sequentially acting GG ‐ NER factors on nucleosomal histone octamers suggests that chromatin provides a recognition scaffold enabling the detection of a subset of CPD s. image Processing of UV ‐induced cyclobutane pyrimidine dimers by global‐genome nucleotide excision repair ( GG ‐ NER ) in the context of nucleosomes is facilitated by the chromatin remodeler CHD 1, whose recruitment by the UV lesion sensor XPC promotes handover to downstream repair factors. UV irradiation leads to increased CHD1 association with chromatin. A subset of chromatin‐bound CHD1 co‐localizes with GG‐NER factors. CHD1 co‐localization to repair sites depends on the XPC lesion sensor. CHD1 promotes nucleosomal lesion handover from XPC to TFIIH. CHD1 depletion decreases excision repair and sensitizes to UV‐induced cytotoxicity.