Human HelQ and DNA polymerase δ interact to halt DNA synthesis and stimulate DNA single-strand annealing

Abstract

DNA strand breaks can be repaired by base pairing with unbroken homologous DNA, forming a template for new DNA synthesis that patches over the break site. In eukaryotes multiple DNA break repair pathways utilize DNA polymerase δ to synthesise new DNA from the end of the broken DNA strand. Here we show that DNA synthesis by human Pol δ is halted by the HelQ DNA repair protein directly targeting isolated Pol δ or Pol δ in complex with PCNA and RPA. The mechanism of inhibition by HelQ is independent of DNA binding and maps to a region of HelQ that also modulates DNA binding by RPA. Interaction of HelQ with the POLD3 subunit of Pol δ stimulated DNA single-strand annealing activity of HelQ. The data suggest a mechanism for HelQ restraining the extent of DNA synthesis across multiple DNA break repair pathways.