We report the identification and expression pattern of a full-length human cDNA and a partial mouse cDNA encoding cyclin B3. Cyclin B3 (CCNB3) is conserved from Caenorhabditis elegans to Homo sapiens and has an undefined meiotic function in female, but not male Drosophila melanogaster. We show that H. sapiens cyclin B3 interacts with cdk2, is localized to the nucleus, and is degraded during anaphase entry after the degradation of cyclin B1. Degradation is dependent on sequences conserved in a destruction box motif. Overexpression of nondegradable cyclin B3 blocks the mitotic cell cycle in late anaphase, and at higher doses it can interfere with progression through G 1 and entry into S phase. H. sapiens cyclin B3 mRNA and protein are detected readily in developing germ cells in the human testis and not in any other tissue. The mouse cDNA has allowed us to further localize cyclin B3 mRNA to leptotene and zygotene spermatocytes. The expression pattern of mammalian cyclin B3 suggests that it may be important for events occurring in early meiotic prophase I.Cyclins are positive regulatory subunits of the cyclin-dependent kinases (cdks).1 Cyclins increase kinase activity by inducing structural changes in the cdk (1). Cyclins also provide substrate binding motifs (2, 3), signals that localize cdks (4, 5), and motifs that allow the incorporation of the cdk into higher order molecular complexes (6, 7). Although first identified as regulators of mitotic cell cycle transitions, cyclin-cdk complexes have other roles: cyclin C-cdk8 and cyclin H-cdk7 regulate transcription as part of the polymerase II holoenzyme (8 -10), pho80-pho85 regulates the localization of the pho4 transcription factor (11), p35-cdk5 regulates neuronal function (12, 13), and cyclin A1, with an unidentified cdk, regulates the pachytene to diplotene transition during male gametogenesis (14).Originally cloned from a chicken cDNA library, cyclin B3 is expressed at very low levels in virally transformed hematopoietic cell lines and early embryonic stages of chicken. When Gallus gallus cyclin B3 is expressed in HeLa cells, it is nuclear, interacts with cdk2 and cdc2, and is associated with a modest histone H1 kinase activity (15). In Drosophila, cyclin B3 is expressed in both mitotic and meiotic cells. In mitotic cells, it is only required when either cyclin A or cyclin B1 is absent. Its abundance is down-regulated during the metaphase to anaphase transition, following degradation of cyclin B1 (16). Overexpression of a nondegradable cyclin B3 is associated with chromatin decondensation defects at the end of mitosis (17). Cyclin B3 is essential for fertility; but unlike cyclin B1 deficiency, infertility of cyclin B3-deficient flies is restricted to the female germ line and does not appear to involve defects in ovary structure or in meiosis I entry (16).We report the cloning of a full-length human cyclin B3 cDNA and a partial mouse cyclin B3 cDNA. Like the previously described chicken and Drosophila homologs, when mammalian cyclin B3 expression is enforced in m...