| ballchen | OKDB#: 2944 |
| Symbols: | ball | Species: | D. melanogaster | ||
| Synonyms: | Ball, BALL, BcDNA:LD09009, CG6386, Dmel\CG6386, nhk-1, NHK-1, NHK1, trip, VRK,VRK, NHK-1, CG6386, BcDNA:LD09009, | Locus: | 97D5-97D5 in Homo sapiens |
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| General Comment | ||||
| General function | Cell cycle regulation | |||
| Comment | ||||
| Cellular localization | Nuclear | |||
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| Ovarian function | ||||
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| Expression regulated by | ||||
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| Ovarian localization | Oocyte | |||
| Comment | The Meiotic Recombination Checkpoint Suppresses NHK-1 Kinase to Prevent Reorganisation of the Oocyte Nucleus in Drosophila. Lancaster OM et al. 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. The conserved kinase NHK-1 is essential for mitotic progression and unifying acentrosomal meiotic spindles in Drosophila melanogaster Cullen CF, et al . Conventional centrosomes are absent from the spindle in female meiosis in many species, but it is not clear how multiple chromosomes form one shared bipolar spindle without centrosomes. We identified a female sterile mutant in which each bivalent chromosome often forms a separate bipolar metaphase I spindle. Unlike wild type, prophase I chromosomes fail to form a single compact structure within the oocyte nucleus, although the integrity of metaphase I chromosomes appears to be normal. Molecular analysis indicates that the mutant is defective in the conserved kinase nucleosomal histone kinase-1 (NHK-1). Isolation of further alleles and RNA interference in S2 cells demonstrated that NHK-1 is also required for mitotic progression. NHK-1 itself is phosphorylated in mitosis and female meiosis, suggesting that this kinase is part of the regulatory system coordinating progression of mitosis and meiosis. | |||
| Follicle stages | ||||
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| Phenotypes | ||||
| Mutations | 0 mutations | |||
| Genomic Region | show genomic region | |||
| Phenotypes and GWAS | show phenotypes and GWAS | |||
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| created: | Nov. 25, 2005, 1:01 a.m. | by: |
hsueh email:
home page: |
| last update: | Nov. 17, 2010, 9:40 a.m. | by: | hsueh email: |
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