Project description:Forkhead transcription factor FHL1 gene was required for replicative lifespan as well as cell proliferation in yeast. In this study, to see how Fhl1p determines the lifespan, we performed a DNA microarray analysis of heterozygous diploid strain deleted for FHL1 and, from the Fhl1p-target genes, screened for a lifespan-related gene. Transcriptomic profiles showed large increases and moderate decreases in transcripts in the fhl1/FHL1 mutant. Pathway analysis suggested upregulation of most of carbon metabolisms (glycolysis, gluconeogenesis, and TCA cycle) and downregulation of translation (ribosomal proteins and translation factors) in the FHL1-deficient mutant. We found a remarkable downregulation of a set of phosphate metabolism genes and ribonucleotide reductase large subunit genes, RNR1 and RNR3. We demonstrated that Fhl1p regulates RNR1 gene transcription to maintain dNTP levels, modulating longevity against replication stress and genomic instability.
