Yeast Genetics and Molecular Biology 2000
University of Washington
Seattle, Washington USA
July 2000

Name: Smith, Jeffrey S
Mailing Address: Biochemistry and Mol. Genetics, University of Virginia, Box 800733, Charlottesville, VA 22908-0733, USA
Email Address: jss5y@virginia.edu
Phone & FAX numbers: 804-243-5864 & 804-924-5069

#026

A phylogenetically conserved NAD + -dependent protein deacetylase activity in the Sir2 protein family.
Jeffrey S. Smith (1), Carrie Baker Brachmann (2), Ivana Celic (2), Margaret A. Kenna (2), Shabazz Muhammad (3), Jose Avalos (3), Cynthia Wolberger (3), Jef D. Boeke (2)
(1) Dept. of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Charlottesville, VA 22908; (2) Dept. of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205; (3) Dept. of Biophysics & Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore MD 21205

The yeast Sir2 protein, required for transcriptional silencing has an NAD+ dependent histone deacetylase (HDA) activity. Yeast extracts contain a NAD+-dependent HDA activity that is eliminated in a yeast strain from which SIR2 and its four homologs have been deleted. This HDA activity is also displayed by purified yeast Sir2p and homologous Archaeal, eubacterial and human proteins and is completely dependent on NAD+ in all species tested. The yeast NPT1 gene, encoding an important NAD+ synthesis enzyme, is required for rDNA and telomeric silencing, and contributes to silencing of the HM loci. Null mutants in this gene have significantly reduced intracellular NAD+ concentrations, and have phenotypes similar to sir2 null mutants. Surprisingly, yeast from which all five SIR2 homologs have been deleted have relatively normal bulk histone acetylation levels. The evolutionary conservation of this regulated activity suggests that the Sir2 protein family represents a set of effector proteins in an evolutionarily conserved signal transduction pathway that monitors cellular energy and redox states.

Return to YGM 2000 Abstract Index