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

Anne Fernandez-Vidal (1, 2) , Laure Guitton-Sert (1, 2) , Jean-Charles Cadoret (3) , Marjorie Drac (4) , Etienne Schwob (4) , Giuseppe Baldacci (3) , Christophe Cazaux (1, 2) , Jean-Sébastien Hoffmann (1, 2)

1 CRCT - Centre de Recherches en Cancérologie de Toulouse
2 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
3 IJM (UMR_7592) - Institut Jacques Monod
4 IGMM - Institut de Génétique Moléculaire de Montpellier

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.

Domaines: Biologie moléculaire; Génétique; Cancer

Anne Fernandez-Vidal, Laure Guitton-Sert, Jean-Charles Cadoret, Marjorie Drac, Etienne Schwob, et al.. A role for DNA polymerase θ in the timing of DNA replication.. Nature Communications, 2014, 5, pp.4285. ⟨10.1038/ncomms5285⟩. ⟨hal-01060296⟩