Figure 8.

Relationship between NIMA and BIMA1^APC3. To help explain why the nimA5 mutation in combination with bimA1^APC3 causes an effective mitotic arrest phenotype, whereas the bimA1^APC3 mutation generates repeating rounds of mitotic oscillation, we propose the following. (A) Substrates of the APC/C, such as cyclin B, Polo-like kinases, and NIMA, accumulate to a threshold during mitosis, which activates the APC/C to trigger their demise and also to exit from mitosis. (B) The bimA1^APC3 mutation increases the threshold of activation of the APC/C. This results in a mitotic delay during which NIMA protein and activity accumulate. When NIMA activity reaches the higher threshold level of activation, the APC/C is activated, and cells can exit mitosis. (C) In the bimA1 + nimA5 double mutant, although p34^cdc2 H1 kinase activity and NIMA5 activity are increased to allow entry into mitosis, the level of NIMA5 activity stays below that required to activate the APC/C. This then causes an extended mitotic arrest, because cells cannot exit mitosis.