MPH1, a yeast gene encoding a DEAH protein, plays a role in protection of the genome from spontaneous and chemically induced damage

We have characterized the MPH1 gene from Saccharomyces cerevisiae. mph1 mut ants display a spontaneous mutator phenotype. Homologs were found in archae a and in the EST libraries of Drosophila, mouse, and man. Mph1 carries the signature motifs of the DEAH family of helicases. Selected motifs were show n to be necessary for MPH1 function by introducing missense mutations. Poss ible indirect effects on translation and splicing were excluded by demonstr ating nuclear localization of the protein and splicing proficiency of the m utant. A mutation spectrum did not show any conspicuous deviations from wil d type except for an underrepresentation of frameshift mutations. The mutat or phenotype Mras dependent on REV3 and RAD6. The mutant was sensitive to M MS, EMS, 4-NQO, and camptothecin, but not to UV light and X rays. Epistasis analyses were carried out with representative mutants from various repair pathways (msh6, mag1, apn1, rad14, rad52, rad6, mms2, and rev3). No epistat ic interactions were found, either for the spontaneous mutator phenotype or for MMS, EMS, and 4-NQO sensitivity. mph1 slightly increased the UV sensit ivity of mmse, rad6, and rad14 mutants, but no effect on X-ray sensitivity was observed. These data suggest that MPH1 is not part of a hitherto known repair pathway. Possible functions are discussed.