Dual requirement for the yeast MMS19 gene in DNA repair and RNA polymerase II transcription

Scott Lauder, Michael Bankmann, Sami N. Guzder, Patrick Sung, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

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, mms19Δ cells do not grow at 37°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 mms19Δ 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 mms19Δ 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.

Original languageEnglish (US)
Pages (from-to)6783-6793
Number of pages11
JournalMolecular and cellular biology
Volume16
Issue number12
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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