biostudies-literatureBalbo Pogliano CSwiss National Science Foundation1333https://www.ebi.ac.uk/biostudies/studies/S-EPMC5673894biostudies-literatureUnknown8(1)Global-genome nucleotide excision repair (GG-NER) prevents ultraviolet (UV) light-induced skin cancer by removing mutagenic cyclobutane pyrimidine dimers (CPDs). These lesions are formed abundantly on DNA wrapped around histone octamers in nucleosomes, but a specialized damage sensor known as DDB2 ensures that they are accessed by the XPC initiator of GG-NER activity. We report that DDB2 promotes CPD excision by recruiting the histone methyltransferase ASH1L, which methylates lysine 4 of histone H3. In turn, methylated H3 facilitates the docking of the XPC complex to nucleosomal histone octamers. Consequently, DDB2, ASH1L and XPC proteins co-localize transiently on histone H3-methylated nucleosomes of UV-exposed cells. In the absence of ASH1L, the chromatin binding of XPC is impaired and iNature communicationsASH1L histone methyltransferase regulates the handoff between damage recognition factors in global-genome nucleotide excision repair.PMC5673894170111Garajova ZBalbo Pogliano CNaegeli HGatti MPenengo LRuthemann PfalseASH1L histone methyltransferase regulates the handoff between damage recognition factors in global-genome nucleotide excision repair.Global-genome nucleotide excision repair (GG-NER) prevents ultraviolet (UV) light-induced skin cancer by removing mutagenic cyclobutane pyrimidine dimers (CPDs). These lesions are formed abundantly on DNA wrapped around histone octamers in nucleosomes, but a specialized damage sensor known as DDB2 ensures that they are accessed by the XPC initiator of GG-NER activity. We report that DDB2 promotes CPD excision by recruiting the histone methyltransferase ASH1L, which methylates lysine 4 of histone H3. In turn, methylated H3 facilitates the docking of the XPC complex to nucleosomal histone octamers. Consequently, DDB2, ASH1L and XPC proteins co-localize transiently on histone H3-methylated nucleosomes of UV-exposed cells. In the absence of ASH1L, the chromatin binding of XPC is impaired and i2017-01-01T00:00:00Z2017 Nov2026-05-06T03:24:41.086Z2019-03-27T03:01:00ZS-EPMC56738942910951110.1038/s41467-017-01080-8