Abstract
The meiotic prophase I to metaphase I transition (G2/MI) involves disassembly of synaptonemal complex (SC), chromatin condensation, and final compaction of morphologically distinct MI bivalent chromosomes. Control of these processes is poorly understood. The G2/MI transition was experimentally induced in mouse pachytene spermatocytes by okadaic acid (OA), and kinetic analysis revealed that disassembly of the central element of the SC occurred very rapidly after OA treatment, before histone H3 phosphorylation on Ser10. These events were followed by relocalization of SYCP3 and final condensation of bivalents. Enzymatic control of these G2/MI transition events was studied using small molecule inhibitors: butyrolactone I (BLI), an inhibitor of cyclin-dependent kinases (CDKs) and ZM447439 (ZM), an inhibitor of aurora kinases (AURKs). The formation of highly condensed MI bivalents and disassembly of the SC are regulated by both CDKs and AURKs. AURKs also mediate phosphorylation of histone H3 in meiosis. However, neither BLI nor ZM inhibited disassembly of the central element of the SC. Thus, despite evidence that the metaphase promoting factor is a universal regulator of the onset of cell division, desynapsis, the first and key step of the G2/MI transition, occurs independently of BLI-sensitive CDKs and ZM-sensitive AURKs.
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Acknowledgments
We thank Dr. Christa Heyting for providing antibodies to SYCP1 and REC8. We are grateful to Drs. John Eppig, Sophie La Salle, Laura Reinholdt, and Lindsay Shopland for providing critical comments on the manuscript. We wish to thank Heather Lothrop for maintaining the mice, and Dr. Jim Denegre and Bobbi-Jo Shirley of the biological imaging facility for assistance. This work was supported by a grant from the NIH to MAH (HD33816) and a Cancer Center Core Grant to The Jackson Laboratory (CA34196).
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Sun, F., Handel, M.A. Regulation of the meiotic prophase I to metaphase I transition in mouse spermatocytes. Chromosoma 117, 471–485 (2008). https://doi.org/10.1007/s00412-008-0167-3
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DOI: https://doi.org/10.1007/s00412-008-0167-3