Although DNA polymerase θ (Pol θ) has been implicated in translesion synthesis and DNA repair, its physiological function remained elusive. Fernandez-Vidal et al. now report that DNA Pol θ has a role in the timing of DNA replication. They showed that in human cells DNA Pol θ is recruited to chromatin in early G1 and interacts with origin recognition complex subunit 2 (ORC2) and ORC4. siRNA-mediated depletion of DNA Pol θ led to increased chromatin loading of minichromosome maintenance (MCM) proteins, which assemble at ORC-binding sites, on chromatin in G1. Although DNA Pol θ depletion did not affect origin density, the authors found genome-wide changes in replication timing (both early to late and late to early) in a subset of replication domains, and overexpression of DNA Pol θ mostly delayed the replication of several domains. Together, these results suggest that DNA Pol θ controls human DNA replication timing by regulating MCM accumulation at pre-replication complexes.
References
Fernandez-Vidal, A. et al. A role for DNA polymerase θ in the timing of DNA replication. Nature Commun. http://dx.doi.org/10.1038/ncomms5285 (2014)
Rights and permissions
About this article
Cite this article
Du Toit, A. DNA Pol θ controls replication timing. Nat Rev Mol Cell Biol 15, 499 (2014). https://doi.org/10.1038/nrm3849
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrm3849