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

Authors: Buzovetsky, Olga; Kwon, Youngho; Pham, Nhung Tuyet; Kim, Claire; Ira, Grzegorz; Sung, Patrick; Xiong, Yong

Published In Cell Rep, (2017 Nov 14)

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.

PubMed ID: 29141206

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 Proteins/chemistry*; Saccharomyces cerevisiae Proteins/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism