NHK-1 phosphorylates BAF to allow karyosome formation in the Drosophila oocyte nucleus.
Accurate chromosome segregation in meiosis requires dynamic changes in chromatin organization. In Drosophila melanogaster, upon completion of recombination, meiotic chromosomes form a single, compact cluster called the karyosome in an enlarged oocyte nucleus. This clustering is also found in humans; however, the mechanisms underlying karyosome formation are not understood. In this study, we report that phosphorylation of barrier to autointegration factor (BAF) by the conserved kinase nucleosomal histone kinase-1 (NHK-1; Drosophila Vrk1) has a critical function in karyosome formation. We find that the noncatalytic domain of NHK-1 is crucial for its kinase activity toward BAF, a protein that acts as a linker between chromatin and the nuclear envelope. A reduction of NHK-1 or expression of nonphosphorylatable BAF results in ectopic association of chromosomes with the nuclear envelope in oocytes. We propose that BAF phosphorylation by NHK-1 disrupts anchorage of chromosomes to the nuclear envelope, allowing karyosome formation in oocytes. These data provide the first mechanistic insight into how the karyosome forms.
The Wellcome Trust Centre for Cell Biology, The University of Edinburgh, Edinburgh EH9 3JR, Scotland, UK.
Oscar M
OM
Lancaster
C Fiona
CF
Cullen
Hiroyuki
H
Ohkura
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000201:enzymology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology*; D008540:Meiosis; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology* / Q000201:enzymology*; D010766:Phosphorylation; D006656:Protamine Kinase / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
C501957:BAF protein, Drosophila; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C506651:Ball protein, Drosophila; D006656:Protamine Kinase