A NIMA HOMOLOG PROMOTES CHROMATIN CONDENSATION IN FISSION YEAST

Entry into mitosis requires p34(cdc2), which activates downstream mito tic events through phosphorylation of key target proteins. In Aspergil lus nidulans, the NIMA protein kinase has been identified as a potenti al downstream target and plays a role in regulating chromatin condensa tion at mitosis, nimA(-) mutants arrest in a state that physically res embles interphase even though p34(cdc2) is fully active. Despite evide nce for the existence of NIMA-like activities in a variety of cell typ es, the only bona fide NIMA homologue that las been identified is the nim-1 gene of Neurospora crassa. We report here the isolation of a fis sion yeast NIMA homologue, and have designated this gene fin1 and the 83 kDa predicted protein p83(fin1). Overexpression of Jin1 promotes pr emature chromatin condensation from any point in the cell cycle indepe ndently of p34(cdc2) function. Like NIR IA, p83(fin1) levels fluctuate through the cell cycle, peaking in mitosis and levels are greatly ele vated by removal of C-terminal PEST sequences. Deletion of fin1 result s in viable but elongated cells, indicative of a cell cycle delay. Gen etic analysis has placed this delay in Gz but, unlike in nimA mutants of Aspergillus, p34(cdc2) activation appears to be delayed. Interactio n of fin1 Delta mutants with other strains defective in chromatin orga nisation also support the hypothesis of p83(fin1) playing a role in th is process at the onset of mitosis, These data indicate that NIMA-rela ted kinases may be a general feature of the cell cycle and chromatin o rganisation at mitosis.