The HO gene of Saccharomyces cerevisiae encodes the endonuclease that initiates mating-type switching. To prevent inopportune switching, HO transcription is restricted to a specific period in the haploid cell cycle, which is just after, and dependent on, the start of the mitotic cell cycle. A repeated promoter element (CACGA4) (refs 7-9) and two trans-acting activators (SWI4 and SWI6) have been identified, which are responsible for the periodic and start-dependent transcription of HO. To understand further the link between start and HO transcription, the SWI6 gene has been cloned and sequenced. The SWI6 protein is similar to the protein in Schizosaccharomyces pombe that is encoded by cdc10 an essential gene specifically required at the start of the cell cycle. The similarity between the SWI6 and cdc10 products, and their common involvement with 'start', suggest that they may share a common mechanism for sensing or executing this critical control step in the cell cycle. The SWI6 and cdc10 proteins also contain two copies of a repeated motif that occurs at least five times in the cytoplasmic domain of the Notch protein of Drosophila melanogaster.