Multiple telophase arrest bypassed (tab) mutants alleviate the essential requirement for Cdc15 in exit from mitosis in S. cerevisiae

Fourteen out of fifteen tab mutants were mapped to three recessive (tab1-tab3) and three dominant (TAB5-TAB7) linkage groups. We show that net1tab2-1 enables growth of tem1Δ, cdc15Δ, dbf2Δ dbf20Δ, and mob1Δ, but not cdc5Δ or cdc14Δ, arguing that whereas the essential task of the first four genes is to promote exit from mitosis, CDC5 possesses additional essential function(s). net1tab2-1 but not CDC14TAB6-1 resulted in a high rate of chromosome loss, indicating that Net1 promotes accurate chromosome segregation in addition to its multiple known roles. Finally, TAB1 was shown to be MTR10, a gene encoding nuclear transport receptor/adaptor. In some of the tab mutants including mtr10tab1-1, defective nuclear export of the ribosomal protein Rpl11b was observed. Furthermore, the transport-defective -31 allele of the karyopherin SRP1, but not the transport competent -49 allele, exhibited a tab phenotype.Transport-defective mutations in two karyopherins can bypass cdc15Δ, suggesting that the function of the MEN is to promote mitotic exit by regulating nuclear transport.In S. cerevisiae, a key event accompanying exit from mitosis is the inactivation of Clb/Cdc28 protein kinase achieved through degradation of Clb and accumulation of the Clb/Cdc28 inhibitor Sic1 (reviewed in [1]). Anaphase-Promoting Complex/Cyclosome (APC/C) ubiquitin ligase and its substrate specific activator Hct1/Cdh1 are required for degradation of Clb2, the major mitotic cyclin in the budding yeast (reviewed in [2]). Whereas hct1Δ and sic1Δ cells appear relatively normal, hct1Δ sic1Δ cells are inviable, presumably due to their inability to extinguish Cdc28 activity in telophase [3].The complexity in the regulation of mitotic exit is underscored by the existence of a set of genes essential for this process, referred to as the "mitotic exit network (MEN)". They encode the GTP-binding protein Tem1 and its putative guanine nucleotide releasing factor Lte1, the dual specificity protein phosphatase Cdc14, prote