Question

Describe how the mitotic spindle, cohesin, APC, separase and securin work together with each other, at the appropriate time in the mitotic phase of the cell cycle, to align the chromosomes along the metaphase plate and how they work together to allow/cause separation of the sister chromatids. Be specific and detailed.

Answer 1

Cohesin holds the sister chromatids together from S phase to late metaphase. Cohesin binds with unreplicated chromosome in late G1 phase while dissociate from chromosome at onset of anaphase in presence of APC. Mitotic spindle apparatus consists of centrosome and microtubules and plays two important roles: organization of chromosome at metaphase plate and seperation of sister chromatids at anaphase. After the disappearance of nuclear envelope, microtubules organise from centromere and penetrate in nuclear region and binds with chromosome. Binding of microtubules to chromosomes is mediated by kinetochore, movement of metaphase chromosome at equatorial plate occurs (short microtubules polymerization and long microtubules depolymerization occurs). During the metaphase all chromosomes are arranged at metaphase plate.

Anaphase includes two major events: 1) Separation of sister chromatids is due to destruction of cohesin protein and destruction of cohesin is catalysed by seperase enzyme. Prior to anaphase securin binds to seperase and inhibits its activity. The APC with specificity factor cdc 20 targets securin for polyubiquitination which then degraded by proteasome. The released separase becomes active and breaks the cross link between sister chromatids. 2) Movement of sister chromatids towards their respective poles due to shortening of kinetochore microtubules.