Requirement of HSM3 gene for spontaneous mutagenesis in Saccharomyces cerevisiae.

In this work, we studied the influence of hsm3 mutation on spontaneous mutagenesis in actively and slowly dividing cells. We demonstrated that the spontaneous mutation rates in the hsm3 mutant and the wild type strain were similar in actively dividing cells. However, during 15-day cultivation of both strains we observed higher accumulation of mutants in the hsm3 strain compared with those in the wild type cells. Effect of accumulation of spontaneous mutants was observed in slowly dividing cells in the rad1, rad2, rad14, rad54, and pms1, but it was absent in the rev3, pol2 and pol3 mutants. Combinations of the hsm3 mutation with the pol3-01, pol2-04 and pms1Delta mutations decreased significantly the level of spontaneous mutagenesis in rapidly growing cells. The hsm3 mutation suppressed synthetic lethality in the hsm3 pol3-01 pms1 triple mutant and dramatically increased the spontaneous mutation rate in comparison with double mutant. The introduction of the hsm3 mutation in NER-mutants led to considerably increasing of the spontaneous mutation level. The double hsm3 rev3, hsm3 rad54 and hsm3 pms1Delta mutants showed lower spontaneous mutation rate compared with the single mutants in rapidly dividing cells. The combination the hsm3 mutation with all studied mutations characterized by different degree of increase of spontaneous mutagenesis in slowly dividing cells. The participation of the Hsm3p in spontaneous mutagenesis in slowly and activity dividing yeast cells is discussed.