Regulation of the meiotic prophase I to metaphase I transition in mouse spermatocytes.
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.
Sun
Fengyun
F
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
Handel
Mary Ann
MA
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D064127:Aurora Kinases; D001549:Benzamides / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D008297:Male; D049469:Meiotic Prophase I / Q000187:drug effects / Q000502:physiology*; D008677:Metaphase / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D013090:Spermatocytes / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D000097722:Cohesins
D015107:4-Butyrolactone; D064127:Aurora Kinases; D001549:Benzamides; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D018844:Cyclin-Dependent Kinases; D004791:Enzyme Inhibitors; D006657:Histones; D019319:Okadaic Acid; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011799:Quinazolines; D000097722:Cohesins; C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; C082868:butyrolactone I