Cloning of a human homolog of the yeast nucleotide excision repair gene MMS19 and interaction with transcription repair factor TFIIH via the XPB and XPD helicases

Nucleotide excision repair (NER) removes UV-induced photoproducts and numer ous other DNA lesions in a highly conserved 'cut-and-paste' reaction that i nvolves approximately 25 core components. In addition, several other protei ns have been identified which are dispensable for NER in vitro but have an undefined role in vivo and may act at the interface of NER and other cellul ar processes. An intriguing example is the Saccharomyces cerevisiae Mms19 p rotein that an unknown dual function in NER and RNA has polymeraser II tran scription. Here we report the cloning:and: characterization of a human homo log, designated haMMS19, that encodes a 1030 amino acid protein with 26% id entity and 51% similarity to S. cerevisiae Mms19p and with a strikingly sim ilar size. The expression profile and nuclear location are consistent with a repair function. Co-immunoprecipitation experiments revealed that hMMS19 directly interacts with the XPB and XPD subunits of NER-transcription facto r TFIIH, These findings extend the conservation of the NER apparatus and th e link between NER and basal transcription and suggest that hMMS19 exerts i ts function in repair and transcription by interacting with:the XPB and XPD helicases.