Kinetoplastid kinetochore proteins KKT14–KKT15 are divergent Bub1/BubR1–Bub3 proteins

Equal segregation of replicated sister chromatids is driven by their biorientation on the mitotic spindle. This is achieved by the attachment of spindle microtubules to the large multi-subunit kinetochore complex assembled on chromosomes. Errors in kinetochore-microtubule attachments trigger the spindle assembly checkpoint (SAC), which functions to delay mitotic progression and grants cells another attempt at establishing correct attachments. The SAC encompasses protein kinases Mps1, Bub1 along with BubR1 (Mad3), Bub3, Mad1 and Mad2. Given that kinetochore and SAC proteins are at the heart of accurate chromosome segregation, they are widely conserved across eukaryotes.

Interestingly, neither canonical kinetochore proteins, nor SAC components are found in the kinetoplastid parasite Trypanosoma brucei. This enigma has fueled work in the Akiyoshi lab, as they try to shed light on the roles of kinetoplastid kinetochore (KKT) proteins and how these parasites adapt to a lack of SAC.

In their recent publication in Open Biology, Ballmer et al. focused on KKT14 and KKT15 proteins. The authors reported that the KKT14 C-terminal domain has structural features and amino acid motifs similar to the Bub1 kinase. This led authors to conclude that KKT14 might be a Bub1 orthologue. Careful observation of the crystal structure also showed that while the KKT14 C-terminal domain adopted a kinase-like fold, it lacked key residues associated with kinase activity and is biochemically inactive. Taking an evolutionary biology approach, this work also proposed that KKT15 is orthologous to Bub3. Importantly, further in vivo experiments showed that KKT14-KKT15 are co-dependent for kinetochore localisation and that they are needed for accurate chromosome segregation in T. brucei.

Taken together, these findings are foundational for future studies aimed to elucidate KKT14 and KKT15’s role in ensuring faithful partitioning of genetic material in T. brucei that is devoid of a conventional SAC.