Progressive cis-inhibition of telomerase upon telomere elongation

EMBO J. 1999 Jun 15;18(12):3509-19. doi: 10.1093/emboj/18.12.3509.

Abstract

In yeast, the constant length of telomeric DNA results from a negative regulation of telomerase by the telomere itself. Here we follow the return to equilibrium of an abnormally shortened telomere. We observe that telomere elongation is restricted to a few base pairs per generation and that its rate decreases progressively with increasing telomere length. In contrast, in the absence of telomerase or in the presence of an over-elongated telomere, the degradation rate linked to the succession of generations appears to be constant, i.e. independent of telomere length. Together, these results indicate that telomerase is gradually inhibited at its site of action by the elongating telomere. The implications of this finding for the dynamics of telomere length regulation are discussed in this study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • DNA Nucleotidyltransferases / genetics
  • DNA Nucleotidyltransferases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Genes, Fungal / genetics
  • Genes, Fungal / physiology
  • Kinetics
  • Models, Genetic
  • Molecular Weight
  • Mutation
  • Rad52 DNA Repair and Recombination Protein
  • Recombination, Genetic
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins*
  • Telomerase / antagonists & inhibitors*
  • Telomerase / genetics
  • Telomerase / metabolism
  • Telomere / genetics*
  • Telomere / metabolism*
  • Templates, Genetic

Substances

  • DNA-Binding Proteins
  • Fungal Proteins
  • RAD50 protein, S cerevisiae
  • RAD52 protein, S cerevisiae
  • Rad52 DNA Repair and Recombination Protein
  • Saccharomyces cerevisiae Proteins
  • DNA Nucleotidyltransferases
  • FLP recombinase
  • Telomerase