The fission yeast homolog of the human transcription factor EAP30 blocks meiotic spindle pole body amplification.
Centrosome aberrations caused by misregulated centrosome maturation result in defective spindle and genomic instability. Here we report that the fission yeast homolog of the human transcription factor EAP30, Dot2, negatively regulates meiotic spindle pole body (SPB, the yeast equivalent of centrosome) maturation. dot2 mutants show excess electron-dense material accumulating near SPBs, which we refer to as aberrant microtubule organization centers (AMtOCs). These AMtOCs assemble multipolar spindles, leading to chromosome missegregation. SPB aberrations were associated with elevated levels of Pcp1, the fission yeast ortholog of pericentrin/kentrin, and reducing pcp1(+) expression significantly suppressed AMtOCs in dot2-439 cells. Our findings, therefore, uncover meiosis-specific regulation of SPB maturation and provide evidence that a member of the conserved EAP30 family is required for maintenance of genome stability through regulation of SPB maturation. EAP30 is part of a transcription factor complex associated with acute myeloid leukemia, so these results may have relevance to human cancer.
Jin
Ye
Y
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Mancuso
Joel J
JJ
Uzawa
Satoru
S
Cronembold
Daniela
D
Cande
W Zacheus
WZ
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D018385:Centrosome / Q000378:metabolism; D043171:Chromosomal Instability; D015825:Chromosomes, Fungal; D006801:Humans; D008540:Meiosis; D046529:Microscopy, Electron, Transmission; D022101:Microtubule-Organizing Center / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016196:S Phase; D012568:Schizosaccharomyces / Q000235:genetics / Q000648:ultrastructure*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; C503313:Dot2 protein, S pombe; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C454082:pcp1 protein, S pombe