Dysfunction of telomeric Cdc13-Stn1-Ten1 simultaneously activates the DNA damage and spindle checkpoints

Telomeres, the ends of eukaryotic linear chromosomes, are composed of repeated DNA sequences and specialized proteins, with the conserved Cdc13/CTC1-Stn1-Ten1 (CST) telomeric comple providing chromosome stability via telomere end-protection and regulation of telomerase accessibility. In the present study, SIZ1 , coding for a SUMO E3 ligase, and TOP2 (Top2 is a SUMO target for Siz1 and Siz2) were isolated as extragenic suppressors of temperature-sensitive mutants of Saccharomyces cerevisiae CST. ten1 - sz, stn1 - sz and cdc13 - sz mutants were next isolated on the basis of being sensitive to intracellular Siz1 dosage. In parallel, strong negative genetic interactions between mutants of CST and septins were identified, septins being noticeably sumoylated through action of Siz1. The temperature-sensitive arrest in these new mutants of CST was dependent on the G2/M Mad2-mediated and Bub2-mediated spindle checkpoints as well as on the G2/M Mec1-mediated DNA damage checkpoint. Our data suggest the existence of yet unknown functions of the telomeric Cdc13-Stn1-Ten1 complex related with mitotic spindle positioning and/or spindle assembly that could be further elucidated by studying these new ten1 - sz, stn1 - sz and cdc13 - sz mutants.