The Set1 methyltransferase opposes Ipl1 aurora kinase functions in chromosome segregation.
A balance in the activities of the Ipl Aurora kinase and the Glc7 phosphatase is essential for normal chromosome segregation in yeast. We report here that this balance is modulated by the Set1 methyltransferase. Deletion of SET1 suppresses chromosome loss in ipl1-2 cells. Conversely, combination of SET1 and GLC7 mutations is lethal. Strikingly, these effects are independent of previously defined functions for Set1 in transcription initiation and histone H3 methylation. We find that Set1 is required for methylation of conserved lysines in a kinetochore protein, Dam1. Biochemical and genetic experiments indicate that Dam1 methylation inhibits Ipl1-mediated phosphorylation of flanking serines. Our studies demonstrate that Set1 has important, unexpected functions in mitosis. Moreover, our findings suggest that antagonism between lysine methylation and serine phosphorylation is a fundamental mechanism for controlling protein function.
Zhang
Ke
K
Program in Genes and Development, Department of Biochemistry and Molecular Biology, M.D. Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA.
Lin
Wenchu
W
Latham
John A
JA
Riefler
Gary M
GM
Schumacher
Jill M
JM
Chan
Clarence
C
Tatchell
Kelly
K
Hawke
David H
DH
Kobayashi
Ryuji
R
Dent
Sharon Y R
SY
D000595:Amino Acid Sequence; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism; D002872:Chromosome Deletion; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D011495:Histone-Lysine N-Methyltransferase; D047908:Intracellular Signaling Peptides and Proteins; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; C116003:DAM1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; D011494:Protein Kinases; D064127:Aurora Kinases; C576961:IPL1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases