Tel1 Activation by the MRX Complex Is Sufficient for Telomere Length Regulation but Not for the DNA Damage Response in Saccharomyces cerevisiae

Genetics. 2019 Dec;213(4):1271-1288. doi: 10.1534/genetics.119.302713. Epub 2019 Oct 23.

Abstract

Previous models suggested that regulation of telomere length in Saccharomyces cerevisiae by Tel1(ATM) and Mec1(ATR) would parallel the established pathways regulating the DNA damage response. Here, we provide evidence that telomere length regulation differs from the DNA damage response in both the Tel1 and Mec1 pathways. We found that Rad53 mediates a Mec1 telomere length regulation pathway but is dispensable for Tel1 telomere length regulation, whereas in the DNA damage response, Rad53 is regulated by both Mec1 and Tel1 Using epistasis analysis with a Tel1 hypermorphic allele, Tel1-hy909, we found that the MRX complex is not required downstream of Tel1 for telomere elongation but is required downstream of Tel1 for the DNA damage response. Our data suggest that nucleolytic telomere end processing is not a required step for telomerase to elongate telomeres.

Keywords: DNA damage response; MRX complex; Tel1; epistasis; telomere.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • DNA Damage*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Multiprotein Complexes / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Telomere / metabolism*
  • Telomere Homeostasis

Substances

  • Intracellular Signaling Peptides and Proteins
  • Multiprotein Complexes
  • Saccharomyces cerevisiae Proteins
  • Protein-Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae