Brachmann C B, Sherman J M, Devine S E, Cameron E E, Pillus L, Boeke J D
Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Genes Dev. 1995 Dec 1;9(23):2888-902. doi: 10.1101/gad.9.23.2888.
Genomic silencing is a fundamental mechanism of transcriptional regulation, 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 telomeric 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 cellular processes.
基因组沉默是转录调控的一种基本机制，但对于保守的沉默机制却知之甚少。我们在此报告酿酒酵母中SIR2沉默基因的四个同源物（HSTs）的发现，以及该基因家族从细菌到哺乳动物的保守性。至少有三个HST基因可在沉默中发挥作用；HST1的过表达可恢复sir2突变体的转录沉默，而hst3 hst4双突变体在端粒沉默方面存在缺陷。此外，HST3和HST4共同促进细胞周期的正常进程、抗辐射能力和基因组稳定性，在沉默与这些基本细胞过程之间建立了新的联系。
