A role for DNA polymerase θ in the timing of DNA replication
| Autor: | Giuseppe Baldacci, Christophe Cazaux, Etienne Schwob, Anne Fernandez-Vidal, Jean-Charles Cadoret, Marjorie Drac, Jean-Sébastien Hoffmann, Laure Guitton-Sert |
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| Přispěvatelé: | Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), La Ligue contre le cancer (Equipe Labellisée 2013), Comité Ile-de-France, GEFLUC grant, Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Toulouse ( CRCT ), Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse] |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
DNA Replication
DNA polymerase DNA polymerase II viruses Origin Recognition Complex General Physics and Astronomy Eukaryotic DNA replication Cell Cycle Proteins [SDV.CAN]Life Sciences [q-bio]/Cancer DNA-Directed DNA Polymerase [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology DNA polymerase delta General Biochemistry Genetics and Molecular Biology Cell Line S Phase [ SDV.CAN ] Life Sciences [q-bio]/Cancer 03 medical and health sciences 0302 clinical medicine Control of chromosome duplication Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology 030304 developmental biology 0303 health sciences [SDV.GEN]Life Sciences [q-bio]/Genetics Multidisciplinary biology Minichromosome Maintenance Proteins DNA replication G1 Phase [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology General Chemistry Processivity Molecular biology Chromatin 030220 oncology & carcinogenesis biology.protein Origin recognition complex [ SDV.GEN ] Life Sciences [q-bio]/Genetics |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2014, 5, pp.4285. ⟨10.1038/ncomms5285⟩ Nat Commun Nat Commun, 2014, 5, pp.4285. ⟨10.1038/ncomms5285 ncomms5285 [pii]⟩ Nature Communications, Nature Publishing Group, 2014, 5, pp.4285. 〈10.1038/ncomms5285〉 www.nature.com/naturecommunications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms5285⟩ |
| Popis: | Although DNA polymerase theta (Pol theta) is known to carry out translesion synthesis and has been implicated in DNA repair, its physiological function under normal growth conditions remains unclear. Here we present evidence that Pol theta plays a role in determining the timing of replication in human cells. We find that Pol theta binds to chromatin during early G1, interacts with the Orc2 and Orc4 components of the Origin recognition complex and that the association of Mcm proteins with chromatin is enhanced in G1 when Pol theta is downregulated. Pol theta-depleted cells exhibit a normal density of activated origins in S phase, but early-to-late and late-to-early shifts are observed at a number of replication domains. Pol theta overexpression, on the other hand, causes delayed replication. Our results therefore suggest that Pol theta functions during the earliest steps of DNA replication and influences the timing of replication initiation. |
| Databáze: | OpenAIRE |
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