Cell cycle arrest determines the intensity of the global transcriptional response of Saccharomyces cerevisiae to ionizing radiation

Whole-genome analysis was performed using DNA microarrays to define the cha nges in the gene expression patterns occurring in Saccharomyces cerevisiae cells exposed to ionizing radiation. The effects of sublethal dose on wild- type, rad53 (enhanced sensitivity to radiation and impaired in a cell cycle damage checkpoint), and rad6 (enhanced sensitivity to radiation and functi onal cell cycle block by radiation) mutant backgrounds and of a higher dose on the wild-type and G(2)-phase-arrested cells were analyzed. Several gene pathways were identified as being implicated in the response to radiation. In particular, the cell cycle blockage that occurred in the wild-type stra in after a high radiation dose and in the rad6 mutant after a lower dose en tailed modifications of defined gene expression patterns, which are describ ed here and are compared with the gene modulation patterns observed in the rad53 strain in the absence of efficient blockage. Loss of the RAD53 functi on caused a major increase in the number of genes modulated by radiation. G iven that Rad53-Sad1p, the protein encoded by RAD53, has functions other th an those directly connected to cell cycle arrest, we determined the gene pa tterns that were modulated upon irradiation of rad53 cells that had been fo rced to arrest in G, phase by nocodazole treatment. These differential whol e-genome analyses shed light on the multiplicity of functions of the pivota l Rad53-Sad1p protein. The results obtained describe how the cells respond to different irradiation conditions by modulating important gene classes, i ncluding those associated with stress defense, ribosomal proteins, histones , ergosterol and GCR1-controlled sugar metabolism. (C) 2001 by Radiation Re search Society.