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PMID: 10512855 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Modulation of life-span by histone deacetylase genes in Saccharomyces cerevisiae.

Molecular biology of the cell ·Vol. 10 ·No. 10 ·1999-10-00 ·Pages 3125-36

Kim S, Benguria A, Lai CY, Jazwinski SM

Abstract

The yeast Saccharomyces cerevisiae has a limited life-span, which is measured by the number of divisions that individual cells complete. Among the many changes that occur as yeasts age are alterations in chromatin-dependent transcriptional silencing. We have genetically manipulated histone deacetylases to modify chromatin, and we have examined the effect on yeast longevity. Deletion of the histone deacetylase gene RPD3 extended life-span. Its effects on chromatin functional state were evidenced by enhanced silencing at the three known heterochromatic regions of the genome, the silent mating type (HM), subtelomeric, and rDNA loci, which occurred even in the absence of SIR3. Similarly, the effect of the rpd3Delta on life-span did not depend on an intact Sir silencing complex. In fact, deletion of SIR3 itself had little effect on life-span, although it markedly accelerated the increase in cell generation time that is observed during yeast aging. Deletion of HDA1, another histone deacetylase gene, did not result in life-span extension, unless it was combined with deletion of SIR3. The hda1Delta sir3Delta resulted in an increase in silencing, but only at the rDNA locus. Deletion of RPD3 suppressed the loss of silencing in rDNA in a sir2 mutant; however, the silencing did not reach the level found in the rpd3Delta single mutant, and RPD3 deletion did not overcome the life-span shortening seen in the sir2 mutant. Deletion of both RPD3 and HDA1 caused a decrease in life-span, which resulted from a substantial increase in initial mortality of the population. The expression of both of these genes declines with age, providing one possible explanation for the increase in mortality during the life-span. Our results are consistent with the loss of rDNA silencing leading to aging in yeast. The functions of RPD3 and HDA1 do not overlap entirely. RPD3 exerts its effect on chromatin at additional sites in the genome, raising the possibility that events at loci other than rDNA play a role in the aging process.

MeSH Terms
Aging Cell Division/genetics DNA, Ribosomal/genetics DNA-Binding Proteins/genetics Fungal Proteins/genetics Gene Deletion Gene Expression Regulation, Fungal Gene Silencing Genes, Fungal Genes, Mating Type, Fungal Genotype Heterochromatin/genetics Histone Deacetylases/genetics Mutation RNA, Messenger/metabolism Saccharomyces cerevisiae/enzymology,genetics Saccharomyces cerevisiae Proteins Silent Information Regulator Proteins, Saccharomyces cerevisiae Sirtuin 2 Sirtuins Time Factors Trans-Activators/genetics Transcription Factors/genetics
Chemicals
DNA, Ribosomal DNA-Binding Proteins Fungal Proteins Heterochromatin RNA, Messenger SIR3 protein, S cerevisiae Saccharomyces cerevisiae Proteins Silent Information Regulator Proteins, Saccharomyces cerevisiae Trans-Activators Transcription Factors RPD3 protein, S cerevisiae SIR2 protein, S cerevisiae Sirtuin 2 Sirtuins Histone Deacetylases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kim S
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans, Louisiana 70112, USA.
Benguria A
Lai C Y
Jazwinski S M
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.10.10.3125
Published
1999-10-00
Pages
3125-36
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC25567
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.10.10.3125 PMC Full Text View journal details
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