TDM1 Regulation Determines the Number of Meiotic Divisions.

Marta Cifuentes,Petra Bulankova,Hirofumi Harashima,Sylvie Jolivet,Wayne Crismani,Laurence Cromer,Raphael Mercier,Karel Riha,Keiko Sugimoto,Arp Schnittger,Charlotte Renne,Yuko Nomura,Hirofumi Nakagami

doi:10.1371/journal.pgen.1005856

Abstract

Cell cycle control must be modified at meiosis to allow two divisions to follow a single round of DNA replication, resulting in ploidy reduction. The mechanisms that ensure meiosis termination at the end of the second and not at the end of first division are poorly understood. We show here that Arabidopsis thaliana TDM1, which has been previously shown to be essential for meiotic termination, interacts directly with the Anaphase-Promoting Complex. Further, mutations in TDM1 in a conserved putative Cyclin-Dependant Kinase (CDK) phosphorylation site (T16-P17) dominantly provoked premature meiosis termination after the first division, and the production of diploid spores and gametes. The CDKA;1-CYCA1.2/TAM complex, which is required to prevent premature meiotic exit, phosphorylated TDM1 at T16 in vitro. Finally, while CYCA1;2/TAM was previously shown to be expressed only at meiosis I, TDM1 is present throughout meiosis. These data, together with epistasis analysis, lead us to propose that TDM1 is an APC/C component whose function is to ensure meiosis termination at the end of meiosis II, and whose activity is inhibited at meiosis I by CDKA;1-TAM-mediated phosphorylation to prevent premature meiotic exit. This provides a molecular mechanism for the differential decision of performing an additional round of division, or not, at the end of meiosis I and II, respectively.

Highlights

In the germ line of sexually reproducing organisms, a specialized cell division—meiosis— ensures ploidy reduction in the gametes
We propose that TDM1 stimulates the anaphase-promoting complex/cyclosome (APC/C) to promote termination of meiosis, this activity of TDM1 being inhibited at meiosis I by CDKA;1-TAM phosphorylation to prevent premature termination of meiosis
To identify genes controlling meiotic progression, a genetic screen was designed based on the idea that mutations that prevent a second meiotic division—such as osd1 and tam–would restore the fertility of mutants that have unbalanced chromosome segregation only at the second meiotic division [18,21]

Summary

Introduction

In the germ line of sexually reproducing organisms, a specialized cell division—meiosis— ensures ploidy reduction in the gametes. The modifications of the cell cycle machinery required for meiosis are not fully understood, but the general perception is that during prophase I, the activity of CDK-cyclin complexes increase slowly until peaking at the onset of the first division. This activity drops when cyclins are degraded by the APC/C to allow the segregation of homologous chromosomes at anaphase I. This decay is not complete, it is sufficient to allow spindle disassembly, entry into a second meiotic division and the avoidance of intervening DNA replication. The proteins and mechanisms that regulate these key meiotic transitions are very diverse among the studied eukaryotes (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster, Mus musculus, Xenopus laevis and Arabidopsis thaliana), even though they all directly modify the CDK-cyclin-APC/C module [5,6,7,8,9,10,11,12,13]

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Results

Conclusion