Dual requirement for the yeast MMS19 gene in DNA repair and RNA polymerase II transcription.
Genetic and biochemical studies of Saccharomyces cerevisiae have indicated the involvement of a large number of protein factors in nucleotide 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 cellular processes. Genetic and biochemical evidence indicates that besides its function in NER, MMS19 also affects RNA polymerase II (Pol II) transcription. mms19delta cells do not grow at 37 degrees C, and mutant extract exhibits a thermolabile defect in Pol II transcription. Thus, Mms19 protein resembles TFIIH in that it is required for both transcription and DNA repair. However, addition of purified Mms19 protein does not alleviate the transcriptional defect of the mms19delta extract, nor does it stimulate the incision of UV-damaged DNA reconstituted from purified proteins. Interestingly, addition of purified TFIIH corrects the transcriptional defect of the mms19delta extract. Mms19 is, however, not a component of TFIIH or of Pol II holoenzyme. These and other results suggest that Mms19 affects NER and transcription by influencing 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.
Lauder
S
S
Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston 77555-1061, USA.
Bankmann
M
M
Guzder
S N
SN
Sung
P
P
Prakash
L
L
Prakash
S
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D004260:DNA Repair / Q000235:genetics*; D004271:DNA, Fungal / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006801:Humans; D008969:Molecular Sequence Data; D012319:RNA Polymerase II / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D014157:Transcription Factors; D014158:Transcription, Genetic
D004271:DNA, Fungal; D005656:Fungal Proteins; C103317:MET18 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D012319:RNA Polymerase II