ACTIVATION OF THE NIMA PROTEIN-KINASE PLAYS A UNIQUE ROLE DURING MITOSIS THAT CANNOT BE BYPASSED BY ABSENCE OF THE BIME CHECKPOINT

Mutation of nim A reversibly arrests cells in late G2 and nim A overexpression promotes premature mitosis. Here we demonstrate that the product of nim A (designated NIMA) has protein kinase activity that can phosphorylate beta-casein but not histone proteins. NIMA kinase activity is cell cycle regulated being 20-fold higher at mitosis when compared to S-phase arrested cells. NIMA activation is normally required in G2 to initiate chromosome condensation, to nucleate spindle pole body microtubules, and to allow an MPM-2 specific mitotic phosphorylation. All three of these mitotic events can occur in the absence of activated NIMA when the bim E gene is mutated (bim E7). However, the bim E7 mutation cannot completely bypass the requirement for nim A during mitosis as entry into mitosis in the absence of NIMA activation results in major mitotic defects that affect both the organization of the nuclear envelope and mitotic spindle. Thus, although nim A plays an essential but limited role during mitosis, mutation of nim A arrests all of mitosis. We therefore propose that mutation of nim A prevents mitotic initiation due to a checkpoint arrest that is negatively mediated by bim E. The checkpoint ensures that mitosis is not initiated until NIMA is mitotically activated.