Multiple kinases inhibit origin licensing and helicase activation to ensure reductive cell division during meiosis

Abstract

Meiotic cells undergo a single round of DNA replication followed by two rounds of chromosome segregation (the meiotic divisions) to produce haploid gametes. Both DNA replication and chromosome segregation are similarly regulated by CDK oscillations in mitotic cells. Yet how these two events are uncoupled between the meiotic divisions is unclear. Using Saccharomyces cerevisiae, we show that meiotic cells inhibit both helicase loading and helicase activation to prevent DNA replication between the meiotic divisions. CDK and the meiosis-specific kinase Ime2 cooperatively inhibit helicase loading, and their simultaneous inhibition allows inappropriate helicase reloading. Further analysis uncovered two previously unknown mechanisms by which Ime2 inhibits helicase loading. Finally, we show that CDK and the polo-like kinase Cdc5 trigger degradation of Sld2, an essential helicase-activation protein. Together, our data demonstrate that multiple kinases inhibit both helicase loading and activation between the meiotic divisions, thereby ensuring reductive cell division.