Figure 2.

Models suggesting APC modulates the SAC or its response to attachment defects. (A) Proposed pathway in wild-type cells. APC promotes stable MT–kinetochore attachment through an unknown mechanism. The SAC monitors MT–kinetochore attachment and only allows mitotic exit once MT occupancy and tension are satisfactory. (a) In Sorger's model (Draviam et al., 2006), SAC function does not require APC. (b) In Näthke's model (Dikovskaya et al., 2007), APC plays a direct role in SAC function. (B) Proposed model accounting for chromosome segregation defects in the absence of APC. Disruption of APC seems to lead to defects in MT–kinetochore attachment, but models differ in what happens downstream. (a) In Sorger's model (Draviam et al., 2006), a functional SAC prolongs metaphase to attempt to correct attachment defects, but some defects remain undetected/uncorrected. This leads to mitotic exit of cells with lagging chromosomes, leading to aneuploidy. (b) In Näthke's model (Dikovskaya et al., 2007), defects in APC lead to compromised SAC function. This leads to mitotic exit without chromosome segregation, generating tetraploid cells.