A genetic screen reveals a role for the late G1-specific transcription factor Swi4p in diverse cellular functions...

The transcription factor Swi4p plays a crucial role in the control of the initiation of the cell cycle in budding yeast. To further understand Swi4p function, we set up a synthetic lethal screen for genes interacting with SWI4. Fourteen conditional mutations which resulted in lethality only in the absence of SWI4 have been isolated. Only two of them were suppressed by ectopic expression of CLN2, indicating that Swi4p is involved in diverse cellular processes in addition to its requirement for CLN1,2 regulation. In most of the mutants a cell cycle phenotype was observed, including defects in G1 progression, budding, the G2/M transition and cytokinesis. In addition, four of the mutations resulted in massive cell lysis at the restrictive temperature, indicating that Swi4p is involved in the maintenance of cell integrity. One of the mutants, rsf1 swi4delta, was characterized in detail and it is defective in cytokinesis at the restrictive temperature. Staining with Calcofluor revealed that the rsf1 swi4delta mutant is impaired in chitin biosynthesis. rsf1 is allelic to the AGM1 gene, coding for N-acetylglucosamine-phosphate mutase, an enzyme involved in the biosynthesis of chitin. A single copy of SWI4 suppressed the cytokinesis defect. The 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 swi4delta mutant phenotype, Swi4p must control some other gene(s) involved in cytokinesis.