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Transcriptional silencing in Saccharomyces cerevisiae at the HM mating-type loci and telomeres occurs through the formation of a heterochromatin-like structure. HM silencing is regulated by cis-acting elements, termed silencers, and by trans-acting factors that bind to the silencers. These factors attract the four SIR (silent information regulator)(More)
Conflicting reports have suggested that the silent information regulator 2 (SIR2) protein family employs NAD(+) to ADP-ribosylate histones [Tanny, J. C., Dowd, G. J., Huang, J., Hilz, H. & Moazed, D. (1999) Cell 99, 735-745; Frye, R. A. (1999) Biochem. Biophys. Res. Commun. 260, 273-279], deacetylate histones [Landry, J., Sutton, A., Tafrov, S. T., Heller,(More)
Transcriptional silencing of the HM mating-type loci in the yeast Saccharomyces cerevisiae is caused by the localized formation of an altered chromatin structure, analogous to heterochromatin in higher eukaryotes. Silencing depends on cis-acting sequences, termed silencers, as well as several trans-acting factors, including histones H4 and H3, proteins RAP1(More)
Studies with yeast DNA topoisomerase mutants indicate that neither topoisomerase I nor II appears to be essential for transcription by RNA polymerase II. However, plasmids carrying transcriptionally active genes are found to be extremely negatively supercoiled when isolated from mutants lacking topoisomerase I. Supercoiling occurs during transcriptional(More)
It has been proposed that cytoplasmic peptide:N-glycanase (PNGase) may be involved in the proteasome-dependent quality control machinery used to degrade newly synthesized glycoproteins that do not correctly fold in the ER. However, a lack of information about the structure of the enzyme has limited our ability to obtain insight into its precise biological(More)
We report the crystal structure of the yeast protein Hpa2 in complex with acetyl coenzyme A (AcCoA) at 2.4 A resolution and without cofactor at 2.9 A resolution. Hpa2 is a member of the Gcn5-related N-acetyltransferase (GNAT) superfamily, a family of enzymes with diverse substrates including histones, other proteins, arylalkylamines and aminoglycosides. In(More)
Previous studies suggest that the yeast SIR1 protein is involved in the establishment of transcriptional silencing at the HM mating-type loci. Here we show that a GAL4 DNA-binding domain-SIR1 hybrid protein (GBD-SIR1), when targeted to an HMR locus containing GAL4-binding sites (UASG), can establish silencing and bypass the requirement for the silencer(More)
The mating type of yeast is determined by the allele, either a or alpha, at the MAT locus. Two other loci, HML and HMR, contain complete copies of the alpha and a genes, respectively, which are not expressed. The four SIR gene products are required in trans for repression of the silent loci, as are cis-acting sites on either side of HML and HMR, about 1000(More)
Escherichia coli deletion mutants lacking DNA topoisomerase I have been identified previously and shown to grow at a normal rate. We show that such strains grow normally only because of spontaneously arising mutations that compensate for the topoisomerase I defect. Several of these compensatory mutations have been found to map at or near the genes encoding(More)
The SIR2 protein family comprises a novel class of nicotinamide-adenine dinucleotide (NAD)-dependent protein deacetylases that function in transcriptional silencing, DNA repair, and life-span extension in Saccharomyces cerevisiae. Two crystal structures of a SIR2 homolog from Archaeoglobus fulgidus complexed with NAD have been determined at 2.1 A and 2.4 A(More)