THE SIR2 GENE FAMILY, CONSERVED FROM BACTERIA TO HUMANS, FUNCTIONS INSILENCING, CELL-CYCLE PROGRESSION, AND CHROMOSOME STABILITY

Genomic silencing is a fundamental mechanism of transcriptional regula tion, yet little is known about conserved mechanisms of silencing. We report here the discovery of four Saccharomyces cerevisiae homologs of the SIR2 silencing gene (HSTs), as well as conservation of this gene family from bacteria to mammals. At least three HST genes can function in silencing; HST1 overexpression restores transcriptional silencing to a sir2 mutant and hst3 hst4 double mutants are defective in telomer ic silencing. In addition, HST3 and HST4 together contribute to proper cell cycle progression, radiation resistance, and genomic stability, establishing new connections between silencing and these fundamental c ellular processes.