MRX protects telomeric DNA at uncapped telomeres of budding yeast cdc13-1 mutants

DNA Repair (Amst). 2006 Jul 13;5(7):840-51. doi: 10.1016/j.dnarep.2006.04.005. Epub 2006 Jun 12.

Abstract

MRX, an evolutionally conserved DNA damage response complex composed of Mre11, Rad50 and Xrs2, is involved in DNA double strand break (DSB) repair, checkpoint activation and telomere maintenance. At DSBs, MRX plays a role in generating single stranded DNA (ssDNA) and signalling cell cycle arrest. Here we investigated whether MRX also contributes to generating ssDNA or signalling cell cycle arrest at uncapped telomeres. To investigate the role of MRX, we generated a conditionally degradable Rad50 protein and combined this with cdc13-1, a temperature sensitive mutation in the Cdc13 telomere capping protein. We show that Rad50 does not contribute to ssDNA generation or cell cycle arrest in response to cdcl3-1 uncapped telomeres. Instead, we find that Rad50 inhibits ssDNA accumulation and promotes cdc13-1 cell viability, consistent with a major role for MRX in telomere capping.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Cycle
  • DNA Repair
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism*
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Endodeoxyribonucleases / chemistry
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism*
  • Exodeoxyribonucleases / chemistry
  • Exodeoxyribonucleases / genetics
  • Exodeoxyribonucleases / metabolism*
  • Genes, Fungal
  • Models, Biological
  • Multiprotein Complexes
  • Mutation
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomere-Binding Proteins / genetics*
  • Telomere-Binding Proteins / metabolism*

Substances

  • Cdc13 protein, S cerevisiae
  • DNA, Fungal
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • RAD50 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Telomere-Binding Proteins
  • XRS2 protein, S cerevisiae
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae