Interplay between nonsense-mediated mRNA decay and DNA damage response pathways reveals that Stn1 and Ten1 are the key CST telomere-cap components.
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.
Institute for Cell and Molecular Biosciences, Newcastle University Medical School, Newcastle upon Tyne NE2 4HH, UK.
Eva-Maria
EM
Holstein
Institute for Cell and Molecular Biosciences, Newcastle University Medical School, Newcastle upon Tyne NE2 4HH, UK.
Kate R M
KR
Clark
Institute for Cell and Molecular Biosciences, Newcastle University Medical School, Newcastle upon Tyne NE2 4HH, UK. Electronic address: david.lydall@newcastle.ac.uk.
David
D
Lydall
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D059365:Nonsense Mediated mRNA Decay; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004277:DNA, Single-Stranded; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C428109:Stn1 protein, S cerevisiae; C512860:TEN1 protein, S cerevisiae; D034501:Telomere-Binding Proteins