Network analysis of the cell cycle response of Saccharomyces cerevisiae to linoleic acid hydroperoxide.
Mark D. Temple, Nazif Alic, Moritz Durchdewald, Chii S. Fong, Ian W. Dawes
Ramaciotti Ctr Gene Func Anal, School of Biotech & Biomol Sci, University of NSW, Sydney, NSW 2052, Australia.
Exposure of wild-type S. cerevisiae to the lipid peroxidation product, linoleic acid hydroperoxide (LoaOOH) is known to provoke a delay in cell cycle progression in late G1. This work follows from a screen of the EUROSCARF Saccharomyces gene deletion mutant collection that demonstrated 256 of the nonessential viable deletants are sensitive to LoaOOH treatment. To further investigate the delay phenotype, 115 of the most sensitivity deletants were additionally screened for their ability to delay in late G1, upon exposure to a low dose of LoaOOH. Over 40 deletants were identified that exhibited absence of G1 cell cycle delay in response to this stress. In addition we present the genome-wide expression response of yeast to LoaOOH exposure. These three distinct data sets; the LoaOOH sensitivity screen, the cycle progression delay screen and the microarray expression profiling, have been analysed independently and as a single organic dataset. Computational network visualisation, filtering and construction played a major role in these analysis in relation to genome wide interactions evident in protein-protein interaction, synthetic lethality and other databases. The results demonstrate that a combinatorial analysis of these data, from the deletant screens and expression profiling, provides a powerful tool to investigating cellular processes such as the poorly understood mechanism of oxidative-damage-induced cell cycle delay.
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