CaMtw1, the Mis12 homolog in the pathogenic yeast candida albicans, plays an essential role in kinetochore assembly and function

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.