Condensin-Mediated Chromosome Folding and Internal Telomeres Drive Dicentric Severing by Cytokinesis
| Autor: | Natalja Barinova, Romain Koszul, Stéphane Marcand, Alice Deshayes, Claire Béneut, Karine Dubrana, Virginia Lopez, Agnès Thierry, Thomas Guerin, Luciana Lazar-Stefanita |
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| Přispěvatelé: | Stabilité génétique, cellules souches et radiations (SGCSR (U_1274 / UMR_E_008)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Régulation spatiale des Génomes - Spatial Regulation of Genomes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was supported by funding to S.M. from Fondation ARC, EDF, CEA Radiobiology call, DRF-Impulsion (4D-DSB-DIC), and ANR (DICENs-ANR-14-CE10-0021-01), to K.D. from the European Research Council under the Seventh Framework Program (FP7/2007 2013/ERC grant agreement 281287), and to R.K. from the European Research Council under the Horizon 2020 Program (ERC grant agreement 260822). T.M.G. was supported by a PhD fellowship from CEA, ANR, and a Fondation ARC young researcher grant., We thank Angela Taddei for lacI, lacI∗∗, and lacO array plasmids and suggestions, Frank Uhlmann and Thomas Kuilman for the G20 plasmid, Helle Ulrich for the AID tool kit, Didier Busso and Eléa Dizet (CIGEX platform) for the Rap1 sites plasmids, Pascale Lesage for the anti-Dps1 antibody, Rémi Montagne for assistance with the Hi-C data, Romain Le Bars (IMAGE-GIF platform) and Lamya Irbah (IRCM microscopy platform) for assistance with higher-resolution microscopy, Dan Throsby for text editing, and John Marko, Damien D’Amours, Sarah Lambert, François-Xavier Barre, Pablo Radicella, Eric Coïc, Laurent Maloisel, Paul-Henri Roméo, Mathias Toulouze, and Maoussi Lhuillier-Akakpo for fruitful discussions and suggestions., ANR-14-CE10-0021,DICENs,Prévention et résolution des chromosomes dicentriques(2014), European Project: 281287,EC:FP7:ERC,ERC-2011-StG_20101109,NDOGS(2012), European Project: 260822,EC:FP7:ERC,ERC-2010-StG_20091118,DICIG(2011), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Condensin
Gene Expression yeast Shelterin Complex MESH: Telomere-Binding Proteins chemistry.chemical_compound Chromosome Breakpoints 0302 clinical medicine MESH: Saccharomyces cerevisiae Proteins Hi-C MESH: Models Genetic DNA Fungal Adenosine Triphosphatases 0303 health sciences biology SMC MESH: Karyotype MESH: Chromosome Breakpoints MESH: Transcription Factors Telomere MESH: Saccharomyces cerevisiae MESH: Chromosomes Fungal Cell biology DNA-Binding Proteins Chromosomes Fungal mutagenesis lacI MESH: Cytokinesis Saccharomyces cerevisiae Proteins MESH: Gene Expression Saccharomyces cerevisiae Karyotype Telomere-Binding Proteins 03 medical and health sciences Dicentric chromosome MESH: Adenosine Triphosphatases Telophase Molecular Biology Mitosis 030304 developmental biology Cytokinesis mitosis Models Genetic [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Cell Biology MESH: Multiprotein Complexes biology.organism_classification telophase abscission MESH: DNA Fungal enzymes and coenzymes (carbohydrates) chemistry Multiprotein Complexes biology.protein MESH: Telomere 030217 neurology & neurosurgery DNA MESH: DNA-Binding Proteins Transcription Factors condensing |
| Zdroj: | Molecular Cell Molecular Cell, 2019, 75 (1), pp.131-144.e3. ⟨10.1016/j.molcel.2019.05.021⟩ Molecular Cell, Elsevier, 2019, 75 (1), pp.131-144.e3. ⟨10.1016/j.molcel.2019.05.021⟩ |
| ISSN: | 1097-2765 1097-4164 |
| Popis: | International audience; In Saccharomyces cerevisiae, dicentric chromosomes stemming from telomere fusions preferentially break at the fusion. This process restores a normal karyotype and protects chromosomes from the detrimental consequences of accidental fusions. Here, we address the molecular basis of this rescue pathway. We observe that tandem arrays tightly bound by the telomere factor Rap1 or a heterologous high-affinity DNA binding factor are sufficient to establish breakage hotspots, mimicking telomere fusions within dicentrics. We also show that condensins generate forces sufficient to rapidly refold dicentrics prior to breakage by cytokinesis and are essential to the preferential breakage at telomere fusions. Thus, the rescue of fused telomeres results from a condensin- and Rap1-driven chromosome folding that favors fusion entrapment where abscission takes place. Because a close spacing between the DNA-bound Rap1 molecules is essential to this process, Rap1 may act by stalling condensins. |
| Databáze: | OpenAIRE |
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