Mms19 protein functions in nucleotide excision repair by sustaining an adequate cellular concentration of the TFIIH component Rad3（PNAS 2008 105 15714–15719） ABSTRACTNucleotide excision repair (NER) is a major cellular defense mechanism against DNA damage. We have investigated the role of Mms19 in NER in the yeast Saccharomyces cerevisiae. NER was deficient in the mms19 deletion mutant cell extracts, which was complemented by the NER/transcription factor TFIIH, but not by purified Mms19 protein. In mms19 mutant cells, protein levels of the core TFIIH component Rad3 (XPD homologue) and Ssl2 (XPB homologue) were significantly reduced by up to 3.5- and 2.2-fold, respectively. The other four essential subunits of the core TFIIH, Tfb1, Tfb2, Ssl1, and Tfb4, and the TFIIK subunits Tfb3, Kin28, andCcl1 of the holo TFIIH were not much affected by Mms19. ElevatingR ad3 protein concentration by overexpressing the protein from ap lasmid under the GAL1 promoter control restored roficient NERi n mms19 mutant cells, as indicated by complementation for UV sensitivity. verexpression of Ssl2 had no effect on repair. Overexpression of Rad3, Ssl2, or both proteins, however, could notc orrect the temperature-sensitive growth defect of mms19 mutantc ells. These results show that Mms19 functions in NER by sustaining an adequate cellular concentration of the TFIIH componentR d 3 and suggest that Mms19 has distinct and separable functions in NER and cell growth, thus implicating Mms19 protein as a novel multifunctional regulator in cells.