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Title: The molecular action of the conserved kinase NHK-1 in karyosome formation during Drosophila female meiosis
Author: Lancaster, Oscar
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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In Drosophila melanogaster females, upon completion of recombination, dramatic reorganisation of the oocyte nucleus occurs and meiotic chromosomes form a compact cluster called the karyosome within the enlarged oocyte nucleus. However, little is known about the mechanism or regulation of karyosome formation. In this thesis, I describe the role of the conserved kinase nucleosomal histone kinase-1 (NHK-1) in karyosome formation. I identify a novel substrate of NHK-1, barrier-to-autointegration factor (BAF), a protein that acts as a linker between the nuclear envelope and chromatin. I find that both a reduction in NHK-1 levels and expression of non-phosphorylatable BAF in oocytes disrupt karyosome formation, resulting in the ectopic association of meiotic chromosomes with the oocyte nuclear envelope. I propose NHK-1 phosphorylates BAF to release meiotic chromosomes from tethering at the nuclear envelope, allowing karyosome formation in the oocyte nucleus. I also show that activation of the meiotic recombination checkpoint maintains the attachment of meiotic chromosomes with the oocyte nuclear envelope and delays post-recombination nuclear reorganisation. Critically, I demonstrate reduction in NHK-1 activity on meiotic recombination checkpoint activation. Therefore, I propose that NHK-1 is a target of the meiotic recombination checkpoint, and has a pivotal role in orchestrating the post-recombination reorganisation of the oocyte nucleus in Drosophila female meiosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available