Disjunction of conjoined twins: Cdk1, Cdh1 and separation of centrosomes

Abstract

Accurate transmission of chromosomes from parent to progeny cell requires assembly of a bipolar spindle. Centrosomes (spindle pole body in yeast) are critical for the biogenesis of this complex mitotic apparatus since they confer bipolarity on the spindle and serve as the site of microtubule polymerization. In each division cycle, the centrosome is duplicated and the sister-centrosomes move away from each other, forming the two poles of the spindle. While the structure and the duplication of centrosomes have been investigated extensively, the understanding of the control of their segregation remains scant. Recent findings are beginning to yield insights into the regulation of centrosome segregation in yeast and its link to the mitotic kinase.

Figure 1

Schematic representation of a Centrosome and Spindle Pole Body (SPB). Shown in boxes are the main components of the centrosome and SPB. Homologous components of the two structure are highlighted in blue.

Figure 2

The Centrosome Duplication Cycle. The centrosome consists of mother and daughter centrioles (green), that are interconnected by an intercentriolar linkage (red) and are embedded in the pericentriolar material (grey) which anchors the microtubules. The mother centriole can be distinguished by the presence of appendages (black lines). (a) During G1, cells lose their orthogonal arrangement. (b) As G1/S, a procentriole (blue) forms perpendicular to each centriole. (c) During S phase, the new centrioles elongate. (d) At G2, the two newly formed centriole pairs disconnect, and (e) by G2/M, the PCM is also divided between the centrioles. (f) At the end of the cycle, the daughter centrioles acquire appendages and behave as a mother centriole during the subsequent cycle.

Figure 3

The Spindle Pole Body (SPB) Duplication Cycle. (a) During G1 (prior to START), the distal end of the half-bridge (red) of the mother SPB (green) acquires a satellite (blue oval). (b) As cells traverse START, the satellite enlarges to form the daughter SPB (blue rectangle). (c) At late S phase, the bridge is severed and (d) the SPBs move apart to form a short spindle. (e) During mitosis, the spindle poles move further apart as the spindle elongates. (f) At the end of the cycle after spindle disassembly, each cell acquires a SPB.

Figure 4

Model depicting role of activated Cdc28 (Cdk1) in SPB separation in budding yeast. Tyrosine dephosphorylation of Cdc28 by Mih1 leads to inactivation of Cdh1 resulting in stabilization of microtubule-associated proteins Cin8, Kip1 and Ase1 whose bundling activity catalyzes SPB separation and formation of the bipolar mitotic spindle.