Reference: Benton MG, et al. (2006) Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation. BMC Genomics 7:305

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Abstract


ABSTRACT: BACKGROUND: One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS) and gamma radiation. RESULTS: Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose response varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes with a biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1) are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The fact that DUN1, RNR2, RNR4, and HUG1 all showed a biphasic response suggests that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response all showed an increased induction with increasing gamma radiation dosage. CONCLUSIONS: Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing new insights into how a cell deals with genotoxicity.

Reference Type
Journal Article
Authors
Benton MG, Somasundaram S, Glasner JD, Palecek SP
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