Abstract:
The precise transmission of the genetic information from one generation to the next during
the mitotic cell cycle is extremely important for a eukaryotic organism. This process
involves faithful duplication of the whole genome during S phase followed by segregation
of the duplicated genome with high fidelity during mitosis. The molecular mechanisms that
ensure equal distribution of duplicated chromosomes in mitosis require proper assembly
of a large multi-protein complex at the centromere (CEN), known as the kinetochore (KT)
(Fig. 1). The primary function of a KT is to attach a chromosome to dynamic plus ends of
spindle microtubules (MTs), a crucial step in segregation of chromosomes. KTs are also
associated with the formation of heterochromatin at the centromeric/pericentric regions
and maintenance of cohesion between sister chromatids till anaphase onset (Cheeseman
and Desai, 2008; Cleveland et al., 2003). Additionally, a KT is involved in recruitment of the
spindle assembly checkpoint (SAC) machinery that monitors the KT-MT attachment and
initiates signals to prevent cell cycle progression if an error persists. Once all the
chromosomes are bi-orientated, separation of two sister chromatids marks the onset of
anaphase. Any defect in the KT structure can disrupt KT-MT interaction that may result in
an unequal distribution of chromosomes leading to aneuploidy.
