THE FISSION YEAST DMA1 GENE IS A COMPONENT OF THE SPINDLE ASSEMBLY CHECKPOINT, REQUIRED TO PREVENT SEPTUM FORMATION AND PREMATURE EXIT FROMMITOSIS IF SPINDLE FUNCTION IS COMPROMISED

Premature initiation of cytokinesis can lead to loss of chromosomes, a nd 'cutting' of the nucleus. Therefore, the proper spatial and tempora l co-ordination of mitosis and cytokinesis is essential for maintainin g the integrity of the genome, The fission yeast cdc16 gene is implica ted both in the spindle assembly checkpoint and control of septum form ation, To identify other proteins involved in these controls, we have isolated multicopy suppressors of the cdc16-116 mutation, and the char acterization of one of these, dma1 (defective in mitotic arrest), is p resented here. dma1 is not an essential gene, but in a dma1 null backg round (dma1-D1) the function of the spindle assembly checkpoint is com promised, If assembly of the spindle is prevented, dma1-D1 cells do no t arrest, the activity of cdc2 kinase decays and cells form a division septum without completing a normal mitosis, dma1-D1 cells also show a n increased rate of chromosome loss during exponential growth, Upon ec topic expression from an inducible promoter, dma1p delays progress thr ough mitosis and inhibits septum formation, giving rise to elongated, multinucleate cells, We propose that dma1 is a component of the spindl e assembly checkpoint, required to prevent septum formation and premat ure exit from mitosis if spindle function is impaired.