Figure 7. Model of how meiotic cells inhibit DNA replication during the MI–MII transition.

(A) Graphical representation of CDK (blue) (Carlile and Amon, 2008) and Ime2 (red) (Berchowitz et al., 2013) kinase activities during meiosis, and how they regulate the chromosome segregation and DNA replication programs. Chromosome segregation is regulated by CDK, whereas DNA replication is regulated by CDK, Ime2, and Cdc5. During the MI-MII transition, CDK activity decreases enough to reset the chromosome segregation program for MII. Although CDK remains active enough to mostly inhibit the DNA replication program, the decreased activity is a significant threat to the inhibition of origin licensing. Ime2 is also mostly sufficient to inhibit Mcm2-7 loading during the MI-MII transition. Cdc5 activity has not been precisely determined and is thus not shown, but it contributes to the inhibition of DNA replication by limiting Mcm2–7 activation. (B) The mechanisms and effector proteins used to inhibit DNA replication during the meiotic divisions. CDK and Ime2 cooperate to inhibit helicase loading by promoting Mcm2–7 nuclear export and the repression of CDC6 by proteolytic degradation and transcriptional inhibition. Additionally, Ime2 phosphorylates and directly inhibits the Mcm2–7 complex, whereas CDK directly inhibits ORC. To inhibit helicase activation, CDK and Cdc5 promote the proteolytic degradation of Sld2.