Analysis of the contribution of Barrier-to-Autointegration Factor (BAF) to centromere function and mitosis progression
[eng] This work is focused on Barrier-to-Autointegration Factor (BAF) protein. BAF is a nuclear envelope (NE) component that binds chromatin and is required for NE reassembly (NER) at mitosis exit. Previous work in our group showed that, in Drosophila, a small fraction of BAF (cenBAF) associates wit...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/184052 |
| Acceso en línea: | https://hdl.handle.net/2445/184052 http://hdl.handle.net/10803/673722 |
| Access Level: | acceso abierto |
| Palabra clave: | Citologia Mitosi Cromosomes Nuclis cel·lulars Cromatina Drosòfila Cytology Mitosis Chromosomes Cell nuclei Chromatin Drosophila |
| Sumario: | [eng] This work is focused on Barrier-to-Autointegration Factor (BAF) protein. BAF is a nuclear envelope (NE) component that binds chromatin and is required for NE reassembly (NER) at mitosis exit. Previous work in our group showed that, in Drosophila, a small fraction of BAF (cenBAF) associates with the centromere. BAF function is regulated by cycles of phosphorylation and dephosphorylation. At the entry of mitosis, BAF is phosphorylated by VRK1/NHK1 kinase and is released from chromatin and the NE. At mitosis exit, protein phosphatase 2A (PP2A) dephosphorylates BAF, which resumes binding to chromatin and promotes NER. Here, we find that cenBAF remains bound to the centromere during mitosis by the action of protein phosphatase 4 (PP4), which is recruited to the centromere by the constitutive centromere component CenpC. At the same time, BAF stabilizes CenpC and PP4 at the centromere forming a functional centromeric network essential for faithful chromosome segregation. Disrupting centromeric localization of PP4 destabilizes cenBAF at centromeres and induces ectopic PP2A-mediated dephosphorylation of free phosphoBAF (pBAF) in mitosis, which results in the accumulation of BAF in a perichromosomal layer surrounding the chromosomes. Concomitantly, NE disassembly/reassembly during mitosis is altered resulting in micronuclei formation and cells with altered NE morphology. This suggests that CenpC, PP4 and cenBAF form a centromeric network that signals pBAF dephosphorylation at mitosis exit by regulating PP2A activity. We also identify T4 and S5 as the main BAF phosphosites in Drosophila and study the actual contribution of PP4 and PP2A to pBAF dephosphorylation. |
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