Title: Understanding the mechanism of chromosome segregation: lessons from diversity

 

Bungo Akiyoshi

Department of Biochemistry, University of Oxford, UK

 

Abstract:

Biologists can learn a lot of lessons from exceptions. Although it was widely assumed that the macromolecular protein complex that drives chromosome segregation (called the kinetochore) consists of proteins that are common to all eukaryotes, no canonical kinetochore components have been identified in a group of organisms called kinetoplastids, which are evolutionarily divergent from yeast and human. To reveal how kinetoplastids achieve chromosome segregation, we identified 25 kinetochore proteins in Trypanosoma brucei (a kinetoplastid parasite that causes African sleeping sickness) and discovered that they constitute kinetochores that are specifically found in kinetoplastids. We are currently characterizing these unconventional kinetochore proteins in vitro and in vivo to understand how they carry out conserved kinetochore functions, such as binding to DNA and microtubules as well as error correction. By understanding how kinetoplastids segregate their chromosomes, we aim to understand fundamental principles of chromosome segregation machinery.

 

Key publications

1. Akiyoshi and Gull (2014) Discovery of unconventional kinetochores in kinetoplastids. Cell 156 (6): 1247–58
2. Ludzia P et al. (2021) Structural characterization of KKT4, an unconventional microtubule-binding kinetochore protein. Structure https://doi.org/10.1016/j.str.2021.04.004
3. Tromer et al. (2021) Repurposing of synaptonemal complex proteins for kinetochores in Kinetoplastida. Open Biology 11: 210049
4.  Marcianò et al. (2021) Unconventional kinetochore kinases KKT2 and KKT3 have unique centromere localization domains. bioRxiv https://doi.org/10.1101/2019.12.13.875419