A role for DNA polymerase θ in the timing of DNA replication

Anne Fernandez-Vidal, Laure Guitton-Sert, Jean-Charles Cadoret, Marjorie Drac, Etienne Schwob, Giuseppe Baldacci, Christophe Cazaux () and Jean-Sébastien Hoffmann ()
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Anne Fernandez-Vidal: Equipe Labellisée Ligue contre le Cancer 2013 INSERM Unit 1037; CNRS ERL 5294; CRCT (Cancer Research Center of Toulouse), BP3028, CHU Purpan
Laure Guitton-Sert: Equipe Labellisée Ligue contre le Cancer 2013 INSERM Unit 1037; CNRS ERL 5294; CRCT (Cancer Research Center of Toulouse), BP3028, CHU Purpan
Jean-Charles Cadoret: Institut Jacques Monod, UMR7592, CNRS and University Paris-Diderot, 15 Rue Hélène Brion, Paris, Cedex 13 75205, France
Marjorie Drac: Institut of Molecular Genetics, CNRS UMR5535 and University of Montpellier
Etienne Schwob: Institut of Molecular Genetics, CNRS UMR5535 and University of Montpellier
Giuseppe Baldacci: Institut Jacques Monod, UMR7592, CNRS and University Paris-Diderot, 15 Rue Hélène Brion, Paris, Cedex 13 75205, France
Christophe Cazaux: Equipe Labellisée Ligue contre le Cancer 2013 INSERM Unit 1037; CNRS ERL 5294; CRCT (Cancer Research Center of Toulouse), BP3028, CHU Purpan
Jean-Sébastien Hoffmann: Equipe Labellisée Ligue contre le Cancer 2013 INSERM Unit 1037; CNRS ERL 5294; CRCT (Cancer Research Center of Toulouse), BP3028, CHU Purpan

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5285

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