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

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

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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. The Pif1-PCNA-Pol δ complex plays an important role in DNA repair through break-induced replication. Buzovetsky et al. determine the crystal structure of a non-canonical PCNA-binding motif in Pif1 bound to PCNA. Biochemical and genetic analysis reveal that the Pif1-PCNA complex enhances Pol δ-mediated DNA synthesis.

Original languageEnglish (US)
Pages (from-to)1707-1714
Number of pages8
JournalCell Reports
Volume21
Issue number7
DOIs
StatePublished - Nov 14 2017

Keywords

  • DNA polymerase δ
  • PCNA
  • PIP box
  • Pif1
  • break induced replication
  • homologous recombination

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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