FEAR but not MEN Genes are Required for Exit from Meiosis I

Abstract

Exit from mitosis is regulated by Cdc14, which plays an essential role intriggering cyclin-dependent kinase inactivation. Throughout most of the cell cycle,Cdc14 is sequestered in the nucleolus where it remains inactive. After thecompletion of anaphase, an essential signaling cascade, named the Mitotic ExitNetwork, or MEN, promotes Cdc14 release. Cdc14 is also released from thenucleolus in early anaphase by another, nonessential, pathway called FEAR(CdcFourteen Early Anaphase Release). Separase (Esp1), polo kinase (Cdc5), thekinetochore protein Slk19, and Spo12, whose molecular function remains unknown,have been identified as members of the FEAR pathway. In meiosis, mutations inCDC14 and its FEAR pathway regulators, CDC5, SLK19, and SPO12, all form ascithat contain only two diploid spores because of a defect in the ability to exit meiosisI. Thus although the FEAR pathway is dispensible for mitotic exit it, is essential formeiosis I exit. The way that the genes of the Mitotic Exit Network contribute tocoordinating meiotic progression is less clear. Here, we explore this issue. Ourresults demonstrate that the orderly transition from meiosis I to meiosis II isaccomplished by eliminating MEN function and using the FEAR pathway tomodulate cyclin dependent kinase activity, in part through the actions of SIC1.