Role for the silencing protein Dot1 in meiotic checkpoint control.
During the meiotic cell cycle, a surveillance mechanism called the "pachytene checkpoint" ensures proper chromosome segregation by preventing meiotic progression when recombination and chromosome synapsis are defective. The silencing protein Dot1 (also known as Pch1) is required for checkpoint-mediated pachytene arrest of the zip1 and dmc1 mutants of Saccharomyces cerevisiae. In the absence of DOT1, the zip1 and dmc1 mutants inappropriately progress through meiosis, generating inviable meiotic products. Other components of the pachytene checkpoint include the nucleolar protein Pch2 and the heterochromatin component Sir2. In dot1, disruption of the checkpoint correlates with the loss of concentration of Pch2 and Sir2 in the nucleolus. In addition to its checkpoint function, Dot1 blocks the repair of meiotic double-strand breaks by a Rad54-dependent pathway of recombination between sister chromatids. In vegetative cells, mutation of DOT1 results in delocalization of Sir3 from telomeres, accounting for the impaired telomeric silencing in dot1.
San-Segundo
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Howard Hughes Medical Institute, Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103, USA.
Roeder
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D000595:Amino Acid Sequence; D002453:Cell Cycle; D015825:Chromosomes, Fungal / Q000235:genetics; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D011495:Histone-Lysine N-Methyltransferase; D008540:Meiosis; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016366:Open Reading Frames; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013172:Spores, Fungal
D016213:Cyclins; D005656:Fungal Proteins; D009687:Nuclear Proteins; C105853:Pch1 protein, S pombe; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C416235:Dot1 protein, S cerevisiae; D011495:Histone-Lysine N-Methyltransferase