A CYTOKINESIS CHECKPOINT REQUIRING THE YEAST HOMOLOG OF AN APC BINDING-PROTEIN

Checkpoint controls ensure that events of the cell-division cycle are completed with fidelity and in the correct order. In budding yeast wit h a mutation in the motor protein dynein, the mitotic spindle is often misaligned and therefore slow to enter the neck between mother cell a nd budding daughter cell. When this occurs, cytokinesis (division of t he cytoplasm into two) is delayed until the spindle is properly positi oned(1). Here we describe mutations that abolish this delay, indicatin g the existence of a new checkpoint mechanism. One mutation lies in th e gene encoding the yeast homologue of EB1, a human protein that binds the adenomatous polyposis coli (APC) protein, a tumour suppressor. EB 1 is located on microtubules of the mitotic spindle and is important i n spindle assembly. EB1 may therefore, by associating with microtubule s, contribute to the sensor mechanism that activates the checkpoint. A nother mutation affects Stt4, a phosphatidylinositol-4-OH kinase. Cold temperature is an environmental stimulus that causes misalignment of the mitotic spindle in yeast and appears to activate this checkpoint m echanism.