Cell cycle regulation of induced mutagenesis in yeast.
The Saccharomyces cerevisiae CDC7 gene encodes a protein kinase that functions in three aspects of DNA metabolism: replication, repair, and meiotic recombination. It is likely that these functions overlap and share common elements. The cell cycle dependence of Cdc7 associated DNA repair was examined by UV irradiating a wild type and hypomutable cdc7-7 strain throughout the cell cycle. Both the wild type strain and the cdc7-7 mutant stain delay entry into S phase by 40-60 min when exposed to UV mutagenesis. Cells in G1 are the most sensitive to lethal UV damage while cells in S phase sustain fewer lethal hits. The yield of mutants is greatest for the CDC7 wild type strain when S phase cells are mutagenized. This peak of induced mutagenesis is absent in the cdc7-7 strain. Cdc7 protein may be required for error-prone DNA repair or for translesion error-prone DNA replication and not for the checkpoints in G1 phase. Because Cdc28 protein kinase and Dbf4 protein, a Cdc7 kinase regulator, are also important for induced mutagenesis and the CDC7 promoter is not induced in response to DNA damage, Cdc7 protein kinase may be regulated post-translationally following DNA damage, in the same manner as it is regulated during the cell cycle.
Ostroff
R M
RM
Department of Biochemistry, Biophysics and Genetics, University of Colorado Health Sciences Center, Denver 80262, USA.
Sclafani
R A
RA
D002453:Cell Cycle / Q000528:radiation effects*; D018797:Cell Cycle Proteins; D004249:DNA Damage; D004260:DNA Repair; D005656:Fungal Proteins / Q000235:genetics; D016193:G1 Phase / Q000528:radiation effects; D016296:Mutagenesis; D011401:Promoter Regions, Genetic / Q000528:radiation effects; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins; D014466:Ultraviolet Rays; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D018797:Cell Cycle Proteins; C088096:Dbf4 protein, S cerevisiae; D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C489404:CDC7 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D001616:beta-Galactosidase