Phenotypes Associated with Saccharomyces cerevisiae Hug1 Protein, a Putative Negative Regulator of dNTP Levels, Reveal Similarities and Differences with Sequence-Related Dif1
2011
Kim, E.M., University of Texas Medical Branch at Galveston, Galveston, TX, USA | Siede, Wolfram, University of North Texas Health Science Center, Fort Worth, TX, USA
Saccharomyces cerevisiae Hugl is a small protein of unknown function that is highly inducible following replication stress and DNA damage. Its deletion suppresses the lethality of deletion of checkpoint kinase Mec1. Although DNA damage responses were largely normal in the HUG1 deletion mutant, we found enhanced resistance towards heat in logarithmic phase. In response to simultaneous carbon and replication stress, overall growth delay and less pseudohyphal filament formation were evident. These novel phenotypes are shared with deletion mutants of the negative regulators of ribonucleotide reductase, Dif1 and Sml1. Microarray analysis showed the influence of Hugl on the expression of a large number of transcripts, including stress-related transcripts. Elevated dNTP levels in hug1Δ cells may result in a stress response reflected by the observed phenotypes and transcript profiles. However, in contrast to a deletion of structurally related Rnr2-Rnr4 subcellular localization is not grossly altered in a Hugl deletion mutant. Thus, although Hugl appears to be derived from the Rnr2-Rnr4 binding region of Dif1, its mechanism of action must be independent of determining the localization of Rnr2-Rnr4.
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