Chromosome segregation at the molecular level
The kinetochore is responsible for coupling chromosomes to spindle microtubules during mitosis and meiosis. However, little is known about the molecular changes occurring during this crucial mechanism. The KINETOCORE (Molecular dissection of the kinetochore – microtubule interface) project has identified several molecular complexes that facilitate chromosomal division fidelity. To do this they designed and developed simpler versions of kinetochores from proteins and DNA that were isolated from the budding yeast, Saccharomyces cerevisiae. Results showed that the use of the microtubule-binding Dam-1 complex was sufficient to enable chromosome segregation with high fidelity. In a native kinetochore, researchers showed that Dam-1 enhances the affinity of the Ndc80 complex for microtubules and enables attachment to growing and shrinking microtubule plus ends. Moreover, there is a high degree of conservation between yeast and human Ndc80. Physically the researchers identified a conserved centromere for the Ndc80 complex. Kinetochores move with the help of a non-canonical kinesin motor that uses a novel motility mechanism to move along microtubules. Other significant molecular complexes include Aurora B which is also highly conserved. Phosphorylation by Aurora B is important for regulating the interaction between the mitotic spindle and controlling Aurora B function itself. The work of KINETOCHORE has featured in high-profile journals. These include The Journal of Cell Biology, Journal of Molecular Biology and Nature Cell Biology.
Keywords
Chromosome segregation, kinetochore, Dam-1 complex, Ndc80, Aurora B
