A GENETIC SCREEN REVEALS A ROLE FOR THE LATE G(1)-SPECIFIC TRANSCRIPTION FACTOR SWI4P IN DIVERSE CELLULAR FUNCTIONS INCLUDING CYTOKINESIS

The transcription factor Swi4p plays a crucial role in the control of the initiation of the cell cycle in budding yeast. To further understa nd Swi4p function, we set up a synthetic lethal screen for genes inter acting with SWI4. Fourteen conditional mutations which resulted in let hality only in the absence of SWI4 have been isolated, Only two of the m were suppressed by ectopic expression of CLN2, indicating that Swi4p is involved in diverse cellular processes in addition to its requirem ent for CLN1,2 regulation. In most of the mutants a cell cycle phenoty pe was observed, including defects in G(1) progression, budding, the G (2)/M transition and cytokinesis, In addition, four of the mutations r esulted in massive cell lysis at the restrictive temperature, indicati ng that Swi4p is involved in the maintenance of cell integrity. One of the mutants, rsf1 swi4 Delta, was characterized in detail and it is d efective in cytokinesis at the restrictive temperature, Staining with Calcofluor revealed that the rsf1 swi4 Delta mutant is impaired in chi tin biosynthesis, rsf1 is allelic to the AGM1 gene, coding for N-acety lglucosamine-phosphate mutase, an enzyme involved in the biosynthesis of chitin. A single copy of SWI4 suppressed the cytokinesis defect, Th e above data suggest that Swi4p has a role in cytokinesis and becomes essential in this process when chitin biosynthesis is compromised, As overexpression or ectopic expression of CLN did not suppress the rsf1 swi4 Delta mutant phenotype, Swi4p must control some other gene(s) inv olved in cytokinesis.