Journal of Microbiology

Research Support, N.I.H., Extramural

Phenotypes Associated with Saccharomyces cerevisiae Hug1 Protein, a Putative Negative Regulator of dNTP Levels, Reveal Similarities and Differences with Sequence-Related Dif1: Eunmi Kim# , Wolfram Siede; J. Microbiol. 2011;49(1):78-85. Published online March 3, 2011; DOI: https://doi.org/10.1007/s12275-011-0200-8

Abstract: Saccharomyces cerevisiae Hug1 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 Hug1 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 Dif1, Rnr2-Rnr4 subcellular localization is not grossly altered in a Hug1 deletion mutant. Thus, although Hug1 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.

Research Support, Non-U.S. Gov't

The Mutation of a Novel Saccharomyces cerevisiae SRL4 Gene Rescues the Lethality of rad53 and lcd1 Mutations by Modulating dNTP Levels: Do-Hee Choi , Young-Mi Oh , Sung-Hun Kwon , Sung-Ho Bae; J. Microbiol. 2008;46(1):75-80.; DOI: https://doi.org/10.1007/s12275-008-0013-6

Abstract: The SRL4 (YPL033C) gene was initially identified by the screening of Saccharomyces cerevisiae genes that play a role in DNA metabolism and/or genome stability using the SOS system of Escherichia coli. In this study, we found that the srl4Δ; mutant cells were resistant to the chemicals that inhibit nucleotide metabolism and evidenced higher dNTP levels than were observed in the wild-type cells in the presence of hydroxyurea. The mutant cells also showed a significantly faster growth rate and higher dNTP levels at low temperature (16 oC) than were observed in the wild-type cells, whereas we detected no differences in the growth rate at 30oC. Furthermore, srl4Δ was shown to suppress the lethality of mutations of the essential S phase checkpoint genes, RAD53 and LCD1. These results indicate that SRL4 may be involved in the regulation of dNTP production by its function as a negative regulator of ribonucleotide reductase.

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