TOWARDS A UNIFYING MODEL FOR THE METAPHASE ANAPHASE TRANSITION/

The term mitosis actually covers a complex sequence of events at the l evel of the cell membrane, the cytoplasm, the nuclear membrane and the chromosomes; recently attention has been focused more and more on the checkpoints that control their orderly progression. The term 'checkpo int' refers here to the inhibitory pathways that coordinate coupling b etween the sequence of events, ensuring dependence of the initiation o f each upon successful completion of others. This paper will mainly fo cus upon the possible checkpoint which controls a brief but essential step, dissociation of the sister chromatids into two identical chromos omes. This step mill be called the metaphase/ anaphase transition, Fir st, the molecular components that are important in metaphase/anaphase transition will be reviewed: accurate segregation of sister chromatids between the daughter cells is dependent on coordinated interaction of centrosomes, centromeres, kinetochores, spindle fibres, topoisomerase s, proteolytic processes and motor proteins. Deficiencies in or impair ment of any of these structures or in their control systems may lead t o a more or less important genomic imbalance. A model combining the ul trastructural components, the molecular components and the controlling molecules will be proposed. The unifying concept emerging from this s ynthesis indicates that sister chromatids separate independently of th e tubulin fibres, as a result of proteolytic processes controlled by t he anaphase promoting complex. The spindle fibres are thus necessary t o move the separated chromatids to the spindle poles but probably not to initiate separation. A number of remaining questions are also highl ighted.