Interplay between nonsense-mediated mRNA decay and DNA damage response pathways reveals that Stn1 and Ten1 are the key CST telomere-cap components

Cell Rep. 2014 May 22;7(4):1259-69. doi: 10.1016/j.celrep.2014.04.017. Epub 2014 May 15.

Abstract

A large and diverse set of proteins, including CST complex, nonsense mediated decay (NMD), and DNA damage response (DDR) proteins, play important roles at the telomere in mammals and yeast. Here, we report that NMD, like the DDR, affects single-stranded DNA (ssDNA) production at uncapped telomeres. Remarkably, we find that the requirement for Cdc13, one of the components of CST, can be efficiently bypassed when aspects of DDR and NMD pathways are inactivated. However, identical genetic interventions do not bypass the need for Stn1 and Ten1, the partners of Cdc13. We show that disabling NMD alters the stoichiometry of CST components at telomeres and permits Stn1 to bind telomeres in the absence of Cdc13. Our data support a model that Stn1 and Ten1 can function in a Cdc13-independent manner and have implications for the function of CST components across eukaryotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Damage*
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism
  • Nonsense Mediated mRNA Decay*
  • Protein Binding
  • Protein Structure, Secondary
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Telomere / genetics*
  • Telomere / metabolism*
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism*
  • Yeasts

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA, Single-Stranded
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Stn1 protein, S cerevisiae
  • TEN1 protein, S cerevisiae
  • Telomere-Binding Proteins