Multiple telophase arrest bypassed (tab) mutants alleviate the essential requirement for Cdc15 in exit from mitosis in S. cerevisiae.
BACKGROUND
The Mitotic Exit Network (MEN) proteins - including the protein kinase Cdc15 and the protein phosphatase Cdc14 - are essential for exit from mitosis in Saccharomyces cerevisiae. To identify downstream targets of the MEN, we sought telophase arrest bypassed (tab) mutations that bypassed the essential requirement for CDC15. Previous studies identified net1(tab2-1) and CDC14(TAB6-1) as mutations in the RENT complex subunits Net1 and Cdc14, respectively, and revealed that the MEN acts by promoting release of Cdc14 from its nucleolar Net1 anchor during anaphase. However, the remaining tab mutants were not characterized.


RESULTS
Fourteen out of fifteen tab mutants were mapped to three recessive (tab1-tab3) and three dominant (TAB5-TAB7) linkage groups. We show that net1(tab2-1) enables growth of tem1Delta, cdc15Delta, dbf2Delta dbf20Delta, and mob1Delta, but not cdc5Delta or cdc14Delta, arguing that whereas the essential task of the first four genes is to promote exit from mitosis, CDC5 possesses additional essential function(s). net1(tab2-1) but not CDC14(TAB6-1) 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 mtr10(tab1-1), 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.


CONCLUSIONS
Transport-defective mutations in two karyopherins can bypass cdc15Delta, suggesting that the function of the MEN is to promote mitotic exit by regulating nuclear transport.
Shou
Wenying
W
Division of Biology, 156-29 Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA. shouw@its.caltech.edu
Deshaies
Raymond J
RJ
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002869:Chromosome Aberrations; D015825:Chromosomes, Fungal / Q000235:genetics; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
C074860:CDC14 protein, S cerevisiae; C082279:CDC15 protein; C093749:CLB2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D019926:Cyclin B; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D005656:Fungal Proteins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017027:Protein Tyrosine Phosphatases; D019204:GTP-Binding Proteins