The Mec1p and Tel1p checkpoint kinases allow humanized yeast to tolerate chronic telomere dysfunctions by suppressing telomere fusions

DNA Repair (Amst). 2009 Feb 1;8(2):209-18. doi: 10.1016/j.dnarep.2008.10.005. Epub 2008 Nov 28.

Abstract

In this work we report that budding yeasts carrying human-type telomeric repeats at their chromosome termini show a chronic activation of the Rad53-dependent DNA damage checkpoint pathway and a G2/M cell cycle delay. Furthermore, in the absence of either TEL1/ATM or MEC1/ATR genes, which encodes phosphatidylinositol 3-kinase-related kinases (PIKKs), we detected telomere fusions, whose appearance correlates with a reduced cell viability and a high rate of genome instability. Based on sequence analysis, telomere fusions occurred primarily between ultrashort telomeres. Microcolony formation assays argue against the possibility that fusion-containing cells are eliminated by PIKK-dependent signalling. These findings reveal that humanized telomeres in yeast cells are sensed as a chronically damaged DNA but do not greatly impair cell viability as long as the cells have a functional DNA damage checkpoint.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chromosomes, Fungal / metabolism
  • DNA Damage
  • DNA-Binding Proteins
  • Genomic Instability
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Microbial Viability
  • Protein Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Telomere / enzymology*
  • Telomere / pathology*

Substances

  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • LIF1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • MEC1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae