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

ABSTRACT: The S. cerevisiae Pif1 helicase functions with DNA polymerase (Pol) ? 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 ? in vitro and also the efficiency of BIR in cells. These results provide insights into the role of the Pif1-PCNA-Pol ? ensemble during DNA break repair by homologous recombination.

SUBMITTER: Buzovetsky O

PROVIDER: S-EPMC5842794 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Buzovetsky Olga O Kwon Youngho Y Pham Nhung Tuyet NT Kim Claire C Ira Grzegorz G Sung Patrick P Xiong Yong Y

Cell reports 20171101 7

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 cons ...[more]

PMID: 29141206

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