The Meiotic Recombination Checkpoint Suppresses NHK-1 Kinase to Prevent Reorganisation of the Oocyte Nucleus in Drosophila
pmid: 21060809
pmc: PMC2965759
The Meiotic Recombination Checkpoint Suppresses NHK-1 Kinase to Prevent Reorganisation of the Oocyte Nucleus in Drosophila
The meiotic recombination checkpoint is a signalling pathway that blocks meiotic progression when the repair of DNA breaks formed during recombination is delayed. In comparison to the signalling pathway itself, however, the molecular targets of the checkpoint that control meiotic progression are not well understood in metazoans. In Drosophila, activation of the meiotic checkpoint is known to prevent formation of the karyosome, a meiosis-specific organisation of chromosomes, but the molecular pathway by which this occurs remains to be identified. Here we show that the conserved kinase NHK-1 (Drosophila Vrk-1) is a crucial meiotic regulator controlled by the meiotic checkpoint. An nhk-1 mutation, whilst resulting in karyosome defects, does so independent of meiotic checkpoint activation. Rather, we find unrepaired DNA breaks formed during recombination suppress NHK-1 activity (inferred from the phosphorylation level of one of its substrates) through the meiotic checkpoint. Additionally DNA breaks induced by X-rays in cultured cells also suppress NHK-1 kinase activity. Unrepaired DNA breaks in oocytes also delay other NHK-1 dependent nuclear events, such as synaptonemal complex disassembly and condensin loading onto chromosomes. Therefore we propose that NHK-1 is a crucial regulator of meiosis and that the meiotic checkpoint suppresses NHK-1 activity to prevent oocyte nuclear reorganisation until DNA breaks are repaired.
- Nagasaki University Japan
- University of Edinburgh United Kingdom
- Wellcome Centre for Cell Biology United Kingdom
- Nagasaki University Japan
Male, Cancer Research, /dk/atira/pure/subjectarea/asjc/1300/1311, /dk/atira/pure/subjectarea/asjc/1300/1312, DNA Repair, Green Fluorescent Proteins, Immunoblotting, Protamine Kinase, QH426-470, Models, Biological, Cell Line, Histones, Genetics, Animals, Drosophila Proteins, Genetics(clinical), DNA Breaks, Double-Stranded, Phosphorylation, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Cell Nucleus, Cell Polarity, /dk/atira/pure/subjectarea/asjc/2700/2716, Meiosis, Drosophila melanogaster, Mutation, Oocytes, Female, /dk/atira/pure/subjectarea/asjc/1300/1306, /dk/atira/pure/subjectarea/asjc/1100/1105, Research Article, DNA Damage
Male, Cancer Research, /dk/atira/pure/subjectarea/asjc/1300/1311, /dk/atira/pure/subjectarea/asjc/1300/1312, DNA Repair, Green Fluorescent Proteins, Immunoblotting, Protamine Kinase, QH426-470, Models, Biological, Cell Line, Histones, Genetics, Animals, Drosophila Proteins, Genetics(clinical), DNA Breaks, Double-Stranded, Phosphorylation, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Cell Nucleus, Cell Polarity, /dk/atira/pure/subjectarea/asjc/2700/2716, Meiosis, Drosophila melanogaster, Mutation, Oocytes, Female, /dk/atira/pure/subjectarea/asjc/1300/1306, /dk/atira/pure/subjectarea/asjc/1100/1105, Research Article, DNA Damage
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