POLD3 as Controller of Replicative DNA Repair

Multiple modes of DNA repair need DNA synthesis by DNA polymerase enzymes. The eukaryotic B-family DNA polymerase complexes delta (Polδ) and zeta (Polζ) help to repair DNA strand breaks when primed by homologous recombination or single-strand DNA annealing. DNA synthesis by Polδ and Polζ is mutagenic, but is needed for the survival of cells in the presence of DNA strand breaks. The POLD3 subunit of Polδ and Polζ is at the heart of DNA repair by recombination, by modulating polymerase functions and interacting with other DNA repair proteins. We provide the background to POLD3 discovery, investigate its structure, as well as function in cells. We highlight unexplored structural aspects of POLD3 and new biochemical data that will help to understand the pivotal role of POLD3 in DNA repair and mutagenesis in eukaryotes, and its impact on human health.