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Published on: September 27, 2015
Suppression of DNA replication via Mos function during meiotic divisions in Xenopus oocytes
N Furuno1, M Nishizawa, K Okazaki
1Division of Molecular Genetics, Kurume University, Fukuoka, Japan.
Abstract:
Meiosis is characterized by the absence of DNA replication between the two successive divisions. In Xenopus eggs, the ability to replicate DNA develops during meiotic maturation, but is normally suppressed until fertilization. Here we show that development of the DNA-replicating ability depends on new protein synthesis during meiosis I, and that mere ablation of the endogenous c-mos product Mos allows maturing oocytes to enter interphase and replicate DNA just after meiosis I. Moreover, we demonstrate that during normal maturation cdc2 kinase undergoes precocious inactivation in meiosis I and then premature reactivation before meiosis II; importantly, this premature cdc2 reactivation absolutely requires Mos function and its direct inhibition by a dominant-negative cdc2 mutant also results in nuclear reformation and DNA replication immediately after meiosis I. These findings indicate that suppression of DNA replication during meiotic divisions in Xenopus oocytes is accomplished by the Mos-mediated premature reactivation of cdc2 kinase. We suggest that these mechanisms for suppressing DNA replication may be specific for meiosis in animal oocytes, and that the ultimate biological function, including the well known cytostatic factor activity, of Mos during meiotic maturation may be to prevent undesirable DNA replication or parthenogenetic activation before fertilization.
Insights
In Xenopus eggs, new proteins made during meiosis I enable DNA replication after the first division. The Mos protein
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Meiosis normally prevents DNA replication between divisions.
- Xenopus oocytes gain DNA replication ability during maturation but it's suppressed until fertilization.
- The c-mos proto-oncogene product (Mos) is crucial for meiotic maturation.
Purpose of the Study:
- To investigate the mechanisms suppressing DNA replication during Xenopus oocyte meiosis.
- To determine the role of Mos and cdc2 kinase in regulating DNA replication during meiosis.
Main Methods:
- Oocyte maturation experiments in Xenopus.
- Ablation of endogenous Mos.
- Expression of dominant-negative cdc2 mutants.
- Analysis of DNA replication and nuclear reformation.
Main Results:
- New protein synthesis during meiosis I is required for DNA replication ability.
- Mos ablation in oocytes allows DNA replication immediately after meiosis I.
- Mos-dependent premature reactivation of cdc2 kinase suppresses DNA replication.
- Inhibition of cdc2 reactivation by dominant-negative mutants also permits DNA replication post-meiosis I.
Conclusions:
- Mos-mediated premature cdc2 kinase reactivation is the key mechanism suppressing DNA replication during Xenopus oocyte meiosis.
- This suppression prevents premature DNA replication and parthenogenetic activation before fertilization.
- These regulatory mechanisms may be specific to animal oocyte meiosis.
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