CELL-CYCLE REGULATION OF INDUCED MUTAGENESIS IN YEAST

The Saccharomyces cerevisiae CDC7 gene encodes a protein kinase that f unctions in three aspects of DNA metabolism: replication, repair, and meiotic recombination. It is likely that these functions overlap and s hare common elements. The cell cycle dependence of Cdc7 associated DNA repair was examined by UV irradiating a wild type and hypomutable cdc 7-7 strain throughout the cell cycle. Both the wild type strain and th e cdc7-7 mutant strain delay entry into S phase by 40-60 min when expo sed 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 cdc 7-7 strain. Cdc7 protein may be required for error-prone DNA repair or for translesion error-prone DNA replication and not for the checkpoin ts in G1 phase. Because Cdc28 protein kinase and Dbf4 protein, a Cdc7 kinase regulator, are also important for induced mutagenesis and the C DC7 promoter is not induced in response to DNA damage, Cdc7 protein ki nase may be regulated post-translationally following DNA damage, in th e same manner as it is regulated during the cell cycle.