Two paralogs involved in transcriptional silencing that antagonistically control yeast life span

In the yeast Saccharomyces cerevisiae, one determinant of aging or life spa n is the accumulation of extrachromosomal copies of rDNA circles in old mot her cells [1]. The production of rDNA circles depends upon intrachromosomal recombination within the rDNA tandem array, a process regulated by the pro tein Sir2 (Sir2p). Together with Sir1p, Sir3p, Sir4p and Orc1p, Sir2p is al so involved in transcriptional silencing of genes at the silent mating-type cassettes, in the rDNA array, and at telomeres. Using a 'triple silencer' strain that can monitor an increase or decrease in gene expression at these three loci, we found that deletion of the ZDS1 gene caused an increase in silencing in the rDNA and at a silent mating-type cassette at the expense o f telomere silencing. The zds1 deletion also resulted in an increase in lif e span and a decrease in Sir3p phosphorylation, In contrast, deletion of it s paralog ZDS2 caused a decrease in rDNA silencing, a decrease in life span and an increase in Sir3p phosphorylation. As Zds2p, but not Zds1p, had str ong two hybrid interactions with Orc1p and the four Sir proteins, Zds1p mig ht indirectly control Sir3p through a Sir3p kinase.