DUAL REQUIREMENT FOR THE YEAST MMS19 GENE IN DNA-REPAIR AND RNA-POLYMERASE-II TRANSCRIPTION

Genetic and biochemical studies of Saccharomyces cerevisiae have indic ated the involvement of a large number of protein factors in nucleotid e excision repair (NER) of UV-damaged DNA, However, how MMS19 affects this process has remained unclear, Here, we report on the isolation of the MMS19 gene and the determination of its role in NER and other cel lular processes. Genetic and biochemical evidence indicates that besid es its function in NER, MMS19 also affects RNA polymerase II (Pol II) transcription. mms19 Delta cells do not grow at 37 degrees C, and muta nt extract exhibits a thermolabile defect in Poi II transcription, Thu s, Mms19 protein resembles TFIIH in that it is required for both trans cription and DNA repair, However, addition of purified Mms19 protein d oes not alleviate the transcriptional defect of the mms19 Delta extrac t, nor does it stimulate the incision of UV-damaged DNA reconstituted from purified proteins. Interestingly, addition of purified TFIIH corr ects the transcriptional defect of the mms19 Delta extract, Mms19 is, however, not a component of TFIIH or of Poi II holoenzyme, These and o ther results suggest that Mms19 affects NER and transcription by influ encing the activity of TFIIH as an upstream regulatory element, It is proposed that mutations in the human MMS19 counterpart could result in syndromes in which both NER and transcription are affected.