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Hyperactivation of the silencing proteins, sir2p and sir3p, causes chromosome loss

Academic Article
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Overview

authors

  • Holmes, S. G.
  • Rose, A. B.
  • Steuerle, K.
  • Saez, Enrique
  • Sayegh, S.
  • Lee, Y. M.
  • Broach, J. R.

publication date

  • March 1997

journal

  • Genetics  Journal

abstract

  • The SIRgene products maintain transcriptional repression at the silent mating type loci and telomeres in Saccharomyces cerevisiae, although no enzymatic or structural activity has been assigned to any of the Sir proteins nor has the role of any of these proteins in transcriptional silencing been clearly defined. We have investigated the functions and interactions of the Sir2, Sir3, and Sir4 proteins by overexpressing them in yeast cells. We find that Sir2p and Sir3p are toxic when overexpressed, while high Sir4p levels have no toxic effect. Epistasis experiments indicate that Sir2p-induced toxicity is diminished in strains lacking the SIR3 gene, while both Sir2p and Sir4p are required for Sir3p to manifest its full toxic effect. In addition, the effects of Sir2 or Sir3 overexpression are exacerbated by specific mutations in the N-terminus of the histone H4 gene. These results are consistent with a model in which Sir2p, Sir3p and Sir4p function as a complex and interact with histones to modify chromatin structure. We find no evidence that toxicity from high levels of the Sir proteins results from widespread repression of transcription. Instead, we find that high levels of Sir2p and/or Sir3p cause a profound decrease in chromosome stability. These results can be appreciated in the context of the effects of Sir2p in histone acetylation and of chromatin structure on chromosome stability.

subject areas

  • Chromosome Deletion
  • DNA-Binding Proteins
  • Fungal Proteins
  • Genes, Lethal
  • Histone Deacetylases
  • Histones
  • Phenotype
  • Saccharomyces cerevisiae
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Sirtuin 2
  • Sirtuins
  • Trans-Activators
  • Transcription, Genetic
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Identity

PubMed Central ID

  • PMC1207846

International Standard Serial Number (ISSN)

  • 0016-6731

PubMed ID

  • 9055071
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Additional Document Info

start page

  • 605

end page

  • 614

volume

  • 145

issue

  • 3

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