Phenotypes associated with Saccharomyces cerevisiae Hug1 protein, a putative negative regulator of dNTP Levels, reveal similarities and differences with sequence-related Dif1.

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 Mecl. 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, Difl and Smll. Microarray analysis showed the influence of Hugl on the expression of a large number of transcripts, including stress-related transcripts. Elevated dNTP levels in hugl Δ cells may result in a stress response reflected by the observed phenotypes and transcript profiles. However, in contrast to a deletion of structurally related Difl, 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 Difl, its mechanism of action must be independent of determining the localization of Rnr2-Rnr4.