Regulation of Heat and Radiation Stress Responses in Yeast by hsp-104

We have investigated the role of heat-shock protein 104 (hsp-104) in the induction of ionizing radiation resistance in yeast. Yeast defective in the production of hsp-104 are constitutively sensitive to killing by heat and are known to be compromised for the induction of thermotolerance. We confirmed that hsp104 yeast mutants are altered in their ability to become thermotolerant by a heat stress. However, we found that the mutant strain did respond to heat shock and increased its resistance to a second lethal heat stress, although the magnitude of the increase was much lower than for the parental wild-type strain. Here we report that the constitutive level of ionizing radiation resistance was higher in the hsp104 mutant compared to wild-type cells and that heat shock induced increased radioresistance in both strains. When radiation was used as the stressing agent, thermal resistance was fully induced in wild-type cells and only slightly induced in the hsp104 mutant. In comparison, radioresistance was induced in both cell strains by a radiation stress. The increased radiation resistance was always slightly higher in the hsp104 mutant but developed with similar kinetics in both cell strains. Entry into stationary growth phase is another event known to induce both thermal tolerance and radiation resistance in yeast. In these experiments, entry into stationary phase induced similar levels of thermal tolerance in the two strains but higher levels of radioresistance in hsp104 mutants. The activation of both resistance mechanisms occurred earlier in the hsp104 mutants compared to wild-type cells. These results show that hsp-104 is not essential for either the process by which the cell recognizes and responds to any of these stresses, or the mechanisms by which the cell actually elevates its resistance to heat and radiation. We conclude, however, that hsp-104 is important in regulating the development and magnitude of induced radiation resistance as well as induced thermal tolerance in yeast.