title: A role for DNA polymerase θ in the timing of DNA replication.
abstract: Although DNA polymerase θ (Pol θ) 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 θ plays a role in determining the timing of replication in human cells. We find that Pol θ 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 θ is downregulated. Pol θ-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 θ overexpression, on the other hand, causes delayed replication. Our results therefore suggest that Pol θ functions during the earliest steps of DNA replication and influences the timing of replication initiation.
authors.affiliation: 1] Equipe Labellisée Ligue contre le Cancer 2013 INSERM Unit 1037; CNRS ERL 5294; CRCT (Cancer Research Center of Toulouse), BP3028, CHU Purpan, Toulouse 31024, France [2] Université Paul Sabatier, University of Toulouse III, Toulouse F-31062, France [3].
authors.forename: Anne
authors.initials: A
authors.lastname: Fernandez-Vidal
authors.affiliation: 1] Equipe Labellisée Ligue contre le Cancer 2013 INSERM Unit 1037; CNRS ERL 5294; CRCT (Cancer Research Center of Toulouse), BP3028, CHU Purpan, Toulouse 31024, France [2] Université Paul Sabatier, University of Toulouse III, Toulouse F-31062, France [3].
authors.forename: Laure
authors.initials: L
authors.lastname: Guitton-Sert
authors.affiliation: 1] Institut Jacques Monod, UMR7592, CNRS and University Paris-Diderot, 15 Rue Hélène Brion, Paris, Cedex 13 75205, France [2].
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Cadoret
authors.affiliation: Institut of Molecular Genetics, CNRS UMR5535 and University of Montpellier, Montpellier 34293, France.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Drac
authors.affiliation: Institut of Molecular Genetics, CNRS UMR5535 and University of Montpellier, Montpellier 34293, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Schwob
authors.affiliation: Institut Jacques Monod, UMR7592, CNRS and University Paris-Diderot, 15 Rue Hélène Brion, Paris, Cedex 13 75205, France.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Baldacci
authors.affiliation: 1] Equipe Labellisée Ligue contre le Cancer 2013 INSERM Unit 1037; CNRS ERL 5294; CRCT (Cancer Research Center of Toulouse), BP3028, CHU Purpan, Toulouse 31024, France [2] Université Paul Sabatier, University of Toulouse III, Toulouse F-31062, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Cazaux
authors.affiliation: 1] Equipe Labellisée Ligue contre le Cancer 2013 INSERM Unit 1037; CNRS ERL 5294; CRCT (Cancer Research Center of Toulouse), BP3028, CHU Purpan, Toulouse 31024, France [2] Université Paul Sabatier, University of Toulouse III, Toulouse F-31062, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hoffmann
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D016193:G1 Phase; D006801:Humans; D064110:Minichromosome Maintenance Proteins / Q000378:metabolism; D051738:Origin Recognition Complex / Q000378:metabolism; D016196:S Phase; D000097462:DNA Polymerase theta
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004259:DNA-Directed DNA Polymerase; D064110:Minichromosome Maintenance Proteins; D051738:Origin Recognition Complex; D000097462:DNA Polymerase theta; C497224:ORC2 protein, human; C109152:ORC4 protein, human