A Role for the Kinetochore COMA Complex in Sensing the Damage in stn1-sz2, a Mutant of the Cdc13-Stn1-Ten1 Telomeric Complex

Telomeres, the ends of linear chromosomes, form a cap composed of specific telomeric DNA asso-ciated with specialized proteins that ensures efficient protection against chromosome degrada-tion and, consequently, overall genome instability. Three main complexes have been implicated in chromosome end protection, namely telomerase, shelterin, and the CST complex (CTC1/Cdc13-STN1-TEN1). In a recent study, we uncovered mutants of the S. cerevisiae CST in which damage was sensed both by the two major spindle checkpoints and the major DNA damage checkpoint. In the best-studied of these mutants, stn1-sz2, the stability and organization of the mitotic tubulin spindle was profoundly affected, as were the organization of the centrosomes and the kineto-chores. Here, we find that the stn1-sz2 mutant is hypersensitive to deletion mutants of two mem-bers of the kinetochores, Ctf19 and Mcm21, which correlated with mis-localization of their asso-ciated subunit in the COMA complex, Okp1, during anaphase. Defects in interactions between the kinetochores and the tubulin spindle are entirely sensed by the SAC (spindle assembly check-point). Here, we find that some of the stn1-sz2 damage is recognized by the Mad2 checkpoint pro-tein independently from the SAC. The data presented here contribute to a better understanding of the damage in stn1-sz2, the prototype of novel mutants of telomeric CST characterized by mitotic-spindle-damage in addition to the classical telomeric-DNA-damage.