Role of the Pif1-PCNA Complex in Pol δ-Dependent Strand Displacement DNA Synthesis and Break-Induced Replication

Cell Rep. 2017 Nov 14;21(7):1707-1714. doi: 10.1016/j.celrep.2017.10.079.

Abstract

The S. cerevisiae Pif1 helicase functions with DNA polymerase (Pol) δ in DNA synthesis during break-induced replication (BIR), a conserved pathway responsible for replication fork repair and telomere recombination. Pif1 interacts with the DNA polymerase processivity clamp PCNA, but the functional significance of the Pif1-PCNA complex remains to be elucidated. Here, we solve the crystal structure of PCNA in complex with a non-canonical PCNA-interacting motif in Pif1. The structure guides the construction of a Pif1 mutant that is deficient in PCNA interaction. This mutation impairs the ability of Pif1 to enhance DNA strand displacement synthesis by Pol δ in vitro and also the efficiency of BIR in cells. These results provide insights into the role of the Pif1-PCNA-Pol δ ensemble during DNA break repair by homologous recombination.

Keywords: DNA polymerase δ; PCNA; PIP box; Pif1; break induced replication; homologous recombination.

MeSH terms

  • Binding Sites
  • DNA Breaks, Double-Stranded
  • DNA Helicases / chemistry*
  • DNA Helicases / metabolism
  • DNA Polymerase III / chemistry*
  • DNA Polymerase III / metabolism
  • DNA Repair
  • DNA Replication*
  • Humans
  • Proliferating Cell Nuclear Antigen / chemistry*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Binding
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Proliferating Cell Nuclear Antigen
  • Saccharomyces cerevisiae Proteins
  • DNA Polymerase III
  • PIF1 protein, S cerevisiae
  • DNA Helicases