The proper division of cells is essential for the production of viable daughter cells. In plants and fungi, the dividing cell produces a cross-wall or septum that bisects the cytoplasm. For separation of the daughter cells, the septum has to be cleaved. To study the regulation of this process, we isolated mutants defective in septum cleavage. The mutants showed highly pleiotropic phenotypes and defined 17 novel genes. The deduced amino acid sequences of the products of the cloned genes exhibited homologies to various transcription regulators of other organisms. The homologies and the pleiotropic effects of the mutations on sexual development, stress response, mitotic stability, septum initiation and septum placement indicated that these genes affect cell separation indirectly, through multifunctional regulatory modules.