Division of Genetics, Department of Cell Biology, University of Salzburg, Salzburg, A-5020 Austria.
G3 (Bethesda). 2013 Dec 9;3(12):2321-33. doi: 10.1534/g3.113.007971.
The heat-shock response in cells, involving increased transcription of a specific set of genes in response to a sudden increase in temperature, is a highly conserved biological response occurring in all organisms. Despite considerable attention to the processes activated during heat shock, less is known about the role of genes in survival of a sudden temperature increase. Saccharomyces cerevisiae genes involved in the maintenance of heat-shock resistance in exponential and stationary phase were identified by screening the homozygous diploid deletants in nonessential genes and the heterozygous diploid mutants in essential genes for survival after a sudden shift in temperature from 30 to 50°. More than a thousand genes were identified that led to altered sensitivity to heat shock, with little overlap between them and those previously identified to affect thermotolerance. There was also little overlap with genes that are activated or repressed during heat-shock, with only 5% of them regulated by the heat-shock transcription factor. The target of rapamycin and protein kinase A pathways, lipid metabolism, vacuolar H(+)-ATPase, vacuolar protein sorting, and mitochondrial genome maintenance/translation were critical to maintenance of resistance. Mutants affected in l-tryptophan metabolism were heat-shock resistant in both growth phases; those affected in cytoplasmic ribosome biogenesis and DNA double-strand break repair were resistant in stationary phase, and in mRNA catabolic processes in exponential phase. Mutations affecting mitochondrial genome maintenance were highly represented in sensitive mutants. The cell division transcription factor Swi6p and Hac1p involved in the unfolded protein response also play roles in maintenance of heat-shock resistance.
细胞的热休克反应,涉及到在应对温度突然升高时特定基因转录的增加,是一种高度保守的生物反应,发生在所有生物体中。尽管人们对热休克过程中激活的过程给予了相当大的关注,但对于基因在应对突然温度升高时的生存中的作用却知之甚少。通过筛选非必需基因的纯合二倍体缺失体和必需基因的杂合二倍体突变体,鉴定了参与细胞指数期和静止期热休克抗性维持的酿酒酵母基因,这些突变体在温度从 30°C 突然升高到 50°C 后,生存能力发生了变化。鉴定出了 1000 多个导致对热休克敏感性改变的基因,它们之间的重叠很少,与以前鉴定出的影响耐热性的基因也很少重叠。与在热休克期间被激活或抑制的基因也几乎没有重叠,只有 5%的基因受到热休克转录因子的调控。雷帕霉素和蛋白激酶 A 途径、脂代谢、液泡 H(+)-ATP 酶、液泡蛋白分选和线粒体基因组维护/翻译对维持抗性至关重要。色氨酸代谢受影响的突变体在两种生长阶段都具有热休克抗性;细胞质核糖体生物发生和 DNA 双链断裂修复受影响的突变体在静止期具有抗性,在指数期的 mRNA 分解代谢过程中具有抗性。影响线粒体基因组维护的突变体在敏感突变体中高度存在。细胞分裂转录因子 Swi6p 和参与未折叠蛋白反应的 Hac1p 也在维持热休克抗性中发挥作用。