The novel roles of centrosomes and kinetochore microtubules in the mitotic spindle function

Abstract

Cell division is crucial for all organisms. Somatic cell division relays on the separation of the genetic material into two daughter cells called mitosis. The structure responsible for the segregation of chromosomes is called the bipolar mitotic spindle. It is composed of centrosomes forming spindle poles, and microtubules emanating from centrosomes, connecting chromosomes to the spindle via kinetochores (kinetochore-microtubules). Here, I have investigated the function of centrosomes and kinetochore microtubules in the mitotic spindle function. I showed that centrosomes regulate the kinetochore-microtubules at both centrosome-proximal (minus) and -distal (plus) microtubule ends. This control depends on the microtubule-length dependent localisation of microtubule-stabilizing protein HURP. I have further used a novel microtubule-destabilizing agent BAL27862 to demonstrate that the number of kinetochore-microtubules attached to chromosomes is dispensable for the mitotic progression but it is crucial for proper chromosome segregation. Overall my research reveals novel mechanisms of mitotic spindle function in human cells.