Abstract
Genomic stability is crucial to the survival and proliferation for all organisms. The genome is subject to various types of DNA damage and chromosome aberration, caused by exogenous and endogenous agents, such as ionizing radiation, alkylating agents and reactive radicals. In Saccharomyces cerevisiae, two members of DNA damage checkpoint pathway, MEC1 and TEL1 (ATR and ATM homolog), have functionally redundant roles in DNA repair. A stress response pathway, HOG1-SWE1 (p38 and WEE1 homolog) MAP kinase pathway, is involved in chromosome integrity caused by unscheduled G2 cell cycle arrest. In this study, we characterized genome stability properties in mec1, tel1, chk1, hog1, and swe1 null mutants. Spontaneous loss of heterozygosity (LOH) increased about 10-fold and 100-fold in the mec1Δ and mec1Δtel1Δ strains, respectively, compared with the wild-type strain. In the chk1Δ, tel1Δ, hog1Δ and swe1Δ strains, the frequency of spontaneous LOH was as low as the wild-type strain. In the chk1Δ strain, however, the rate of chromosome loss was higher than the wild-type strain. On the other hand, in the hog1Δ and swe1Δ strains, chromosome loss frequency was exhibited low levels compared with wild-type strain. We further showed that mec1Δ, mec1Δtel1Δ mutants did not increased rates of UV-induced gene conversion. These results suggest that G2 checkpoint activated by MAP kinase pathway was involved in the formation of spontaneously and UV-induced chromosome aberrations, such as chromosome loss, while MEC1 damage checkpoint pathway activated by UV-induced DNA damage was involved in DNA damage repair. It was reported that LOH was not induced by MMS treatment and x-ray irradiation in the mec1Δ strain. However, UV irradiation could induce LOH in the mec1Δ strain. We therefore assume that UV-induced LOH elevation was caused by the recombination through the RAD51 and RAD52, activated by UV-induced pyrimidine dimers.
