Spo13/ MEIKIN ensures a Two‐Division meiosis by preventing the activation of APC / C Ama1 at meiosis I

Abstract

Genome haploidization at meiosis depends on two consecutive nuclear divisions, which are controlled by an oscillatory system consisting of Cdk1‐cyclin B and the APC/C bound to the Cdc20 activator. How the oscillator generates exactly two divisions has been unclear. We have studied this question in yeast where exit from meiosis involves accumulation of the APC/C activator Ama1 at meiosis II. We show that inactivation of the meiosis I‐specific protein Spo13/MEIKIN results in a single‐division meiosis due to premature activation of APC/C Ama1 . In the wild type, Spo13 bound to the polo‐like kinase Cdc5 prevents Ama1 synthesis at meiosis I by stabilizing the translational repressor Rim4. In addition, Cdc5‐Spo13 inhibits the activity of Ama1 by converting the B‐type cyclin Clb1 from a substrate to an inhibitor of Ama1. Cdc20‐dependent degradation of Spo13 at anaphase I unleashes a feedback loop that increases Ama1's synthesis and activity, leading to irreversible exit from meiosis at the second division. Thus, by repressing the exit machinery at meiosis I, Cdc5‐Spo13 ensures that cells undergo two divisions to produce haploid gametes. image Deletion of SPO13 in yeast and Meikin in male mammals results in exit from meiosis after a single division. A complex of Spo13 and polo‐like kinase ensures a two‐division meiosis by preventing premature activation of the APC/C Ama1 ubiquitin ligase at meiosis I. Yeast spo13Δ mutants undergo only one division because they prematurely synthesize and activate Ama1, an APC/C co‐activator dedicated to exit from meiosis. Spo13 prevents a kinase cascade consisting of Cdc5/Plk1, Ime2, and CK1 δ /Hrr25 from mediating degradation of the translational repressor Rim4. By phosphorylating the B‐type cyclin Clb1, the Cdc5‐Spo13 kinase converts Cdk1‐Clb1 from a target into an inhibitor of Ama1‐dependent proteolysis.