![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 10, Issue 10, 3125-3136, October 1999
Department of Biochemistry and Molecular Biology, Louisiana State
University Medical Center, New Orleans, Louisiana 70112
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 rpd3
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 hda1 sir3 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 rpd3 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.
Corresponding author. E-mail address:
sjazwi{at}lsumc.edu.
This article has been cited by other articles:
|
|
 |
|
  W. C. Burhans and M. Weinberger DNA replication stress, genome instability and aging Nucleic Acids Res., December 3, 2007; 35(22): 7545 - 7556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. B. Tahara, M. H. Barros, G. A. Oliveira, L. E. S. Netto, and A. J. Kowaltowski Dihydrolipoyl dehydrogenase as a source of reactive oxygen species inhibited by caloric restriction and involved in Saccharomyces cerevisiae aging FASEB J, January 1, 2007; 21(1): 274 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Jambunathan, A. W. Martinez, E. C. Robert, N. B. Agochukwu, M. E. Ibos, S. L. Dugas, and D. Donze Multiple Bromodomain Genes Are Involved in Restricting the Spread of Heterochromatic Silencing at the Saccharomyces cerevisiae HMR-tRNA Boundary Genetics, November 1, 2005; 171(3): 913 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. L. Chua, S. Channeliere, E. Mott, and J. C. Gray The bromodomain protein GTE6 controls leaf development in Arabidopsis by histone acetylation at ASYMMETRIC LEAVES1 Genes & Dev., September 15, 2005; 19(18): 2245 - 2254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhao, H. Sun, J. Lu, X. Li, X. Chen, D. Tao, W. Huang, and B. Huang Lifespan extension and elevated hsp gene expression in Drosophila caused by histone deacetylase inhibitors J. Exp. Biol., February 15, 2005; 208(4): 697 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ferrarini, L. Bertelli, J. Feala, A. D. McCulloch, and G. Paternostro A more efficient search strategy for aging genes based on connectivity Bioinformatics, February 1, 2005; 21(3): 338 - 348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Bauer, S. Goupil, G. B. Garber, and S. L. Helfand An accelerated assay for the identification of lifespan-extending interventions in Drosophila melanogaster PNAS, August 31, 2004; 101(35): 12980 - 12985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. S. Burger and D. E. L. Promislow Sex-Specific Effects of Interventions That Extend Fly Life Span Sci. Aging Knowl. Environ., July 14, 2004; 2004(28): pe30 - pe30. [Abstract] [Full Text]
|
|
|
|
|
|
C. Borghouts, A. Benguria, J. Wawryn, and S. M. Jazwinski Rtg2 Protein Links Metabolism and Genome Stability in Yeast Longevity Genetics, February 1, 2004; 166(2): 765 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Falcon and J. P. Aris Plasmid Accumulation Reduces Life Span in Saccharomyces cerevisiae J. Biol. Chem., October 24, 2003; 278(43): 41607 - 41617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Bitterman, O. Medvedik, and D. A. Sinclair Longevity Regulation in Saccharomyces cerevisiae: Linking Metabolism, Genome Stability, and Heterochromatin Microbiol. Mol. Biol. Rev., September 1, 2003; 67(3): 376 - 399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tatar Unearthing Loci That Influence Life Span Sci. Aging Knowl. Environ., March 5, 2003; 2003(9): pe5 - 5. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Tatar, A. Bartke, and A. Antebi The Endocrine Regulation of Aging by Insulin-like Signals Science, February 28, 2003; 299(5611): 1346 - 1351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Benguria, P. Hernandez, D. B. Krimer, and J. B. Schvartzman Sir2p suppresses recombination of replication forks stalled at the replication fork barrier of ribosomal DNA in Saccharomyces cerevisiae Nucleic Acids Res., February 1, 2003; 31(3): 893 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rogina, S. L. Helfand, and S. Frankel Longevity Regulation by Drosophila Rpd3 Deacetylase and Caloric Restriction Science, November 29, 2002; 298(5599): 1745 - 1745. [Full Text] [PDF]
|
|
|
|
|
|
C.-Y. Lai, E. Jaruga, C. Borghouts, and S. M. Jazwinski A Mutation in the ATP2 Gene Abrogates the Age Asymmetry Between Mother and Daughter Cells of the Yeast Saccharomyces cerevisiae Genetics, September 1, 2002; 162(1): 73 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. M. Hoopes, M. Budd, W. Choe, T. Weitao, and J. L. Campbell Mutations in DNA Replication Genes Reduce Yeast Life Span Mol. Cell. Biol., June 15, 2002; 22(12): 4136 - 4146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Merker and H. L. Klein hpr1{Delta} Affects Ribosomal DNA Recombination and Cell Life Span in Saccharomyces cerevisiae Mol. Cell. Biol., January 15, 2002; 22(2): 421 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kaeberlein, M. McVey, and L. Guarente Using Yeast to Discover the Fountain of Youth Sci. Aging Knowl. Environ., October 3, 2001; 2001(1): pe1 - 1. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. Baidyaroy, G. Brosch, J.-h. Ahn, S. Graessle, S. Wegener, N. J. Tonukari, O. Caballero, P. Loidl, and J. D. Walton A Gene Related to Yeast HOS2 Histone Deacetylase Affects Extracellular Depolymerase Expression and Virulence in a Plant Pathogenic Fungus PLANT CELL, July 1, 2001; 13(7): 1609 - 1624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. JAZWINSKI Metabolic Control and Gene Dysregulation in Yeast Aging Ann. N.Y. Acad. Sci., June 1, 2000; 908(1): 21 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Loewith, J. S. Smith, M. Meijer, T. J. Williams, N. Bachman, J. D. Boeke, and D. Young Pho23 Is Associated with the Rpd3 Histone Deacetylase and Is Required for Its Normal Function in Regulation of Gene Expression and Silencing in Saccharomyces cerevisiae J. Biol. Chem., June 22, 2001; 276(26): 24068 - 24074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-L. Kang, S. Benzer, and K.-T. Min Life extension in Drosophila by feeding a drug PNAS, January 22, 2002; 99(2): 838 - 843. [Abstract] [Full Text] [PDF]
|
|
