4 research outputs found
SCF-Fbxo42 promotes synaptonemal complex assembly by downregulating PP2A-B56
No full textMeiosis creates genetic diversity by recombination and segregation of chromosomes. The synaptonemal complex assembles during meiotic prophase I and assists faithful exchanges between homologous chromosomes, but how its assembly/disassembly is regulated remains to be understood. Here we report how two major post-translational modifications, phosphorylation and ubiquitination, co-operate to promote synaptonemal complex assembly. We found that the ubiquitin ligase complex SCF is important for assembly and maintenance of the synaptonemal complex in Drosophila female meiosis. This function of SCF is mediated by two substrate recognising F-box proteins, Slmb/βTrcp and Fbxo42. SCF-Fbxo42 downregulates the phosphatase subunit PP2A-B56, which is important for synaptonemal complex assembly and maintenance
Ubiquitin ligases regulate chromatin organisation during meiotic prophase in Drosophila melanogaster
No full textMeiosis 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
SCEP3 initiates synapsis and implements crossover interference in <i>Arabidopsis</i>
No full textThe synaptonemal complex (SC) is a meiosis-specific tripartite proteinaceous structure that regulates the number and positions of crossovers (COs). Here we characterize SCEP3, a new Arabidopsis SC component that is essential for CO assurance, promoting positive CO interference and preventing negative CO interference. SCEP3 localizes to the chromosome axes as numerous foci at leptotene, of which a small proportion cluster as large foci that initiate synapsis. SCEP3 then relocates to the central region of the SC as ZYP1 polymerizes. In the absence of SCEP3, homologues align but do not synapse. In the scep3 mutants, COs increase in number towards the chromosome ends and are more likely to cluster together. SCEP3 encodes an 801-amino-acid intrinsically disordered protein that is structurally similar to SIX6OS1 in mammals and SYP-4 in nematodes, containing phenylalanine repeats at the amino terminus and a carboxy-terminal coiled-coil, suggesting that it is a fundamentally conserved SC component across kingdoms
SCEP3 initiates synapsis and implements crossover interference in Arabidopsis
No full textThe synaptonemal complex (SC) is a meiosis-specific tripartite proteinaceous structure that regulates the number and positions of crossovers (COs). Here we characterize SCEP3, a new Arabidopsis SC component that is essential for CO assurance, promoting positive CO interference and preventing negative CO interference. SCEP3 localizes to the chromosome axes as numerous foci at leptotene, of which a small proportion cluster as large foci that initiate synapsis. SCEP3 then relocates to the central region of the SC as ZYP1 polymerizes. In the absence of SCEP3, homologues align but do not synapse. In the scep3 mutants, COs increase in number towards the chromosome ends and are more likely to cluster together. SCEP3 encodes an 801-amino-acid intrinsically disordered protein that is structurally similar to SIX6OS1 in mammals and SYP-4 in nematodes, containing phenylalanine repeats at the amino terminus and a carboxy-terminal coiled-coil, suggesting that it is a fundamentally conserved SC component across kingdoms.</p
