Short telomeres induce a DNA damage response in Saccharomyces cerevisiae

Mol Biol Cell. 2003 Mar;14(3):987-1001. doi: 10.1091/mbc.02-04-0057.

Abstract

Telomerase-deficient Saccharomyces cerevisiae cells show a progressive decrease in telomere length. When grown for several days in log phase, the tlc1Delta cells initially display wild-type growth kinetics with subsequent loss of growth potential after which survivors are generated via RAD52-dependent homologous recombination. We found that chromosome loss in these telomerase-deficient cells only increased after a significant decline in growth potential of the culture. At earlier stages of growth, as the telomerase-deficient cells began to show loss of growth potential, the cells arrested in G2/M and showed RNR3 induction and Rad53p phosphorylation. These responses were dependent on RAD24 and MEC1, suggesting that short telomeres are recognized as DNA damage and signal G2/M arrest.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Cycle / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Division / physiology
  • DNA Damage
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Protein-Serine-Threonine Kinases
  • Rad52 DNA Repair and Recombination Protein
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Telomere / metabolism*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • RAD24 protein, S cerevisiae
  • RAD52 protein, S cerevisiae
  • Rad52 DNA Repair and Recombination Protein
  • Saccharomyces cerevisiae Proteins
  • MEC1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • Telomerase