Limiting DNA polymerase delta alters replication dynamics and leads to a dependence on checkpoint activation and recombination-mediated DNA repair

DNA polymerase delta (Pol ? ) plays several essential roles in eukaryotic replication and repair. At the fork, Pol is responsible for synthesis processing of lagging-strand. origins, has been proposed to initiate leading-strand by extending first Okazaki fragment. Destabilizing mutations human subunits cause stress syndromic immunodeficiency. Analogously, reduced levels Saccharomyces cerevisiae lead pervasive genome instability. Here, we analyze how depletion impacts origin firing lagging-strand during elongation vivo S . By analyzing nascent products, observe a genome-wide change both establishment progression replication. S-phase slowed depletion, with globally slower progression. We find that no other than capable synthesizing substantial amount DNA, even when severely limiting. also characterize impact impaired on integrity increased ssDNA damage limiting; these defects strict dependence checkpoint signaling resection-mediated repair pathways cellular viability.