Molecular Mechanisms of Stopping and Starting the Cell Cycle

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Meiotic cell cycle in oocytes is characterized by the arrest and release at G2-phase of immature oocytes, lack of S-phase in interkinesis period and the second arrest after the completion of meiosis. To elucidate the molecular mechanisms underlying these characteristics, we have found the followings in the project.1. G2-phase arrest and its release : G2-phase arrest in immature starfish oocytes is supported by Weel-like kinase, but not Weel itself. At the release, both phosphorylation of Cdc25 phosphatase and suppression of Weel-like kinase occur independently of cdc2 kinase activity, resulting in the initial activation of cdc2 kinase.2. Lack of S-phase in interkinesis period : We have developed from Xenopus oocyte extracts a cell-free system, "meiotic extracts", which mimics meiotic M/M transition. Successful N/N transition depends on both Mos, whose downstream is known MAP kinase and unknow pathway, and low protein levels of Weel.3. GI-phase arrest in mature eggs : In mature starfish eggs, MAP kinase activity is necessary and sufficient for the G1-phase arrest and suppression of S-phase. As an upstream of MAP kinase, we have isolated starfish Mos for the first time in invertebrate oocytes which do not arrest at the second meiotic metaphase. Comparison among Xenopus, mouse and starfish oocytes reveals that a conserved role of Mos might be to ensure the successful entry into meiosis II, thus preventing parthenogenetic activation.