Ubiquitin ligases regulate chromatin organisation during meiotic prophase in Drosophila melanogaster
Item statusRestricted Access
Embargo end date31/07/2022
Silva, Pedro Barbosa
Barbosa Silva, Pedro
Meiosis creates genetic diversity by recombination and segregation of chromosomes. Meiotic errors can lead to chromosome missegregation and consequently infertility or birth defects. In Drosophila oocytes chromosomes undergo crucial reorganisation events during meiotic prophase to prepare for proper recombination and chromosome segregation. However, the molecular mechanisms regulating chromatin reorganisation remain poorly understood. The importance of post-translational modifications during chromatin rearrangements has been shown across many species. Here, I report the role of the SCF complex, an E3 ubiquitin ligase, in synaptonemal complex assembly and karyosome formation in Drosophila oocytes. The SCF complex is constituted by SkpA, Cul-1, Roc and a substrate recognising protein (F-box). I have identified two specific F-box proteins, Slmb and CG6758, to be required for the karyosome formation and synaptonemal complex assembly. Moreover, I identified PP2A as an interactor of the F-box protein CG6758 and described the role of CG6758 in regulating the amount of PP2A-B56 subunit. Thus, in this work, I have demonstrated that the SCF-CG6758 protein complex downregulates the phosphatase subunit PP2A-B56, which is required for proper synaptonemal complex and karyosome formation. To further determine the role of ubiquitination during meiotic prophase, I carried out an RNAi screen for ubiquitin-associated proteins. I found that multiple other ubiquitin ligases have an important role in karyosome formation. However, only the components of the neddylation cycle, an important regulator of the SC, showed to be required for synaptonemal complex assembly and karyosome formation. Overall, my findings uncover a novel role for the ubiquitin ligase SCF in meiotic prophase. Moreover, it opens a new line of inquiry about the importance of post-translational modifications in synaptonemal complex assembly and karyosome formation.