Interplay between Nonsense-Mediated mRNA Decay and DNA Damage Response Pathways Reveals that Stn1 and Ten1 Are the Key CST Telomere-Cap Components

• STN1 and TEN1 play more critical roles in budding yeast than CDC13
• Several routes bypass cdc13Δ, but not stn1Δ or ten1Δ
• Components of CST bind telomeres with different ratios
• NMD pathways affect accumulation of ssDNA at uncapped telomeres

SummaryA 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.

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