Mutation of fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication.

Entry into mitosis in fission yeast is controlled by the p34cdc2 protein kinase, which is activated by cdc25+ and inhibited by wee1+. In "wee" mutants one or the other of these controls is circumvented resulting in advancement of mitosis. We report that dependence of mitosis on DNA synthesis is lost in wee mutants in which cdc25+ control is circumvented either by mutations in cdc2+ or by overproduction of cdc25+. In contrast, dependence is maintained when the wee1+ control is bypassed. We propose that cdc25+ activity requires completion of earlier cell-cycle events such as DNA synthesis, and thus links p34cdc2 kinase activation to completion of these earlier events. Constitutive expression of cdc25+ homologs could explain why mitosis is not dependent on DNA replication in some early embryos.