RAD6gene is involved in heat shock induction of bleomycin resistance inSaccharomyces cerevisiae

Abstract

Cells react to environmental and endogenous challenges such as high temperature, reactive oxygen species, DNA damage, and nutrient starvation by activating several defense mechanisms known as stress responses. An important feature is the overlap between different stress responses that contributes at least in part to the phenomenon of cross-protection. We previously demonstrated that pretreatment with a heat shock (HS) induces resistance to the lethal and mutagenic effects of the antineoplastic drug Bleomycin (BLM) in wild-type Saccharomyces cerevisiae. At the DNA level, the HS resulted in more efficient repair of BLM-induced DNA damage. In the present study, we have investigated the mechanisms involved in this HS-induced BLM resistance. Since the RAD6 gene is involved in the ubiquitin system and DNA repair, we analyzed the effects of HS on the lethality of BLM in a rad6Delta (ubc2) mutant strain of S. cerevisiae. The rad6Delta mutant was more sensitive to the lethal effects of BLM than wild-type yeast and HS had no effect on the lethality of BLM in the mutant. Analysis of cell proliferation kinetics indicated that the HS-induced cell cycle delay observed in the wild-type yeast was absent in the rad6Delta mutant strain. BLM treatment impaired mutant cell proliferation, and HS had no effect on the delayed cell kinetics of the mutant. In addition, pulsed-field electrophoresis of chromosomes damaged by BLM indicated that there was very little recovery from damage in the mutant after 24 hr of incubation in BLM-free nutrient medium, and that HS had little effect on the recovery. These data indicate that the RAD6 gene is involved in the HS-induced BLM resistance observed in the isogenic wild-type strain.

Lethal and mutagenic interactions between γ-rays, cisplatin and etoposide at the cellular and molecular levels

“…On the other side, the lethal additivity and the low mutagenic interaction observed in case of Pt þ E combination (Figures 2c, 3b, 4b, and 5b) can be explained by independent error-prone processing of induced damage, most probably error-prone excision repair (MMR), NHEJ and postreplicative errorprone repair (Keszenman et al 2005). The contribution of NHEJ in the repair of DNA damage produced by etoposide in Saccharomyces has been previously determined (Malik et al 2006).…”

Symbiont‐specific responses to environmental cues in a threesome lichen symbiosis

“…Escherichia coli it has been shown that the presence of antibiotic resistance genes probably has been induced by adaptation to stress (like thermal stress) as tolerance towards antibiotics underlies similar mechanisms as tolerance towards heat (Cruz-Loya et al, 2019) This could potentially explain why a gene encoding a bleomycin resistance protein was upregulated at elevated temperatures in the cyanobiont of P. britannica. In addition, Keszenman et al (2000Keszenman et al ( , 2005 have demonstrated that the upregulation of bleomycin resistance genes is a side effect of heat stress in S. cerevisiae, as the yeast cells proved to be resistant to bleomycin treatment after having been exposed to heat stress. This correlation between heat stress and bleomycin resistance is probably the result of cross-linking of DNA repair mechanisms (Keszenman et al, 2000(Keszenman et al, , 2005.…”

“…In addition, Keszenman et al (2000Keszenman et al ( , 2005 have demonstrated that the upregulation of bleomycin resistance genes is a side effect of heat stress in S. cerevisiae, as the yeast cells proved to be resistant to bleomycin treatment after having been exposed to heat stress. This correlation between heat stress and bleomycin resistance is probably the result of cross-linking of DNA repair mechanisms (Keszenman et al, 2000(Keszenman et al, , 2005. A potential role of bleomycin-resistance genes in DNA repair has already been proposed in previous studies on E. coli (Blot et al, 1991).…”

HDF1 and RAD17 Genes are Involved in DNA Double-strand Break Repair in Stationary Phase Saccharomyces cerevisiae

“…Quantification is possible after laser absorbance analysis [14]. Estimation of mean values of induced DNA double-strand breaks (DBSs) and of corresponding standard deviations were based on the Poisson distribution as: −L Ix/Io, where Ix corresponds to the integral (surface) of a given chromosomal band in the densitograms after treatment and Io is the integral of the same chromosomal band in the respective control sample [9,[13][14][15][16].…”