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Abstract

During meiosis, a single round of DNA replication is followed by two consecutive rounds of chromosome segregation. While the suppression of DNA replication between meiosis I and –II is one of the defining features of meiosis, its mechanism has remained unclear. The control of DNA replication has been studied extensively in proliferating cells in which DNA replication during S phase strictly alternates with chromosome segregation at mitosis. The mechanism ensuring that each sequence is replicated only once per cell cycle is based on the dual function of Cdk1: low Cdk1 activity after mitosis allows the establishment of prereplicative complexes at replication origins (origin licensing). Activation of Cdk1 at the onset of S phase then initiates DNA replication (origin firing) by converting the pre-replicative complex to the post-replicative complex. Since high Cdk1 activity inhibits the reformation of pre-replicative complexes, the next round of DNA replication cannot occur until after Cdk1 has been inactivated during mitosis when replicated chromosomes segregate. However, applying this concept to meiosis would trigger an additional round of DNA replication because Cdk1 activity drops and then re-appears between meiosis I and –II. Two ideas have been proposed to solve this problem: in Xenopus eggs, Cdk1 activity is reduced rather than completely destroyed between meiosis I and –II, while in yeast, a Cdk1-related kinase, called Ime2, was thought to prevent origin relicensing at anaphase I. We have tested these ideas by artificially inactivating and then reactivating Cdk1 and Ime2 at anaphase I. Remarkably, DNA replication was not induced even when both kinases were simultaneously inhibited and re-activated at anaphase I. Thus, additional mechanisms must prevent DNA replication between meiosis I and –II.