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PMID: 10880470 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Genetics ·Vol. 155 ·No. 3 ·2000-07-00 ·Pages 1069-81

Scheller J, Schürer A, Rudolph C, Hettwer S, Kramer W

Abstract

We have characterized the MPH1 gene from Saccharomyces cerevisiae. mph1 mutants display a spontaneous mutator phenotype. Homologs were found in archaea and in the EST libraries of Drosophila, mouse, and man. Mph1 carries the signature motifs of the DEAH family of helicases. Selected motifs were shown to be necessary for MPH1 function by introducing missense mutations. Possible indirect effects on translation and splicing were excluded by demonstrating nuclear localization of the protein and splicing proficiency of the mutant. A mutation spectrum did not show any conspicuous deviations from wild type except for an underrepresentation of frameshift mutations. The mutator phenotype was dependent on REV3 and RAD6. The mutant was sensitive to MMS, 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 epistatic interactions were found, either for the spontaneous mutator phenotype or for MMS, EMS, and 4-NQO sensitivity. mph1 slightly increased the UV sensitivity of mms2, 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.

MeSH Terms
Carrier Proteins/metabolism,pharmacology DEAD-box RNA Helicases DNA Damage/genetics DNA Mutational Analysis DNA Repair/genetics DNA-Directed DNA Polymerase/metabolism Fungal Proteins/metabolism Genome, Fungal Mutagenicity Tests Mutation/genetics RNA Helicases/genetics Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins Sequence Homology, Amino Acid
Chemicals
Carrier Proteins Fungal Proteins Saccharomyces cerevisiae Proteins DNA-Directed DNA Polymerase REV3 protein, S cerevisiae MPH1 protein, S cerevisiae DEAD-box RNA Helicases RNA Helicases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Scheller J
Abteilung Molekulare Genetik und Präparative Molekularbiologie, Institut für Mikrobiologie und Genetik, Georg-August-Universität Göttingen, 37077 Göttingen, Germany.
Schürer A
Rudolph C
Hettwer S
Kramer W
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1093/genetics/155.3.1069
Published
2000-07-00
Pages
1069-81
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1461162
Subset
IM
External Links
PubMed source DOI: 10.1093/genetics/155.3.1069 PMC Full Text View journal details
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