Cell cycle studies have revealed mechanisms that prevent cell division if DNA fails to be completely replicated or sustains damage. Here we focus on the evidence from yeast genetics that the wee1 and mik1 tyrosine kinases cooperate in the inhibitory phosphorylation of cdc2p, and the possibility that these kinases function in pathways that ensure the integrity of the genome prior to cell division. We also review the progress in cloning and analysing wee1-like tyrosine kinases from higher eukaryotes, and the evidence for and against their functioning in ensuring DNA replication prior to mitosis. Finally, we discuss the genes involved in these feedback controls and suggest that wee1p and mik1p might be the ultimate effectors that prevent mitosis when a checkpoint is triggered.