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Publication Detail

Title: A novel role of the Dna2 translocase function in DNA break resection.

Authors: Miller, Adam S; Daley, James M; Pham, Nhung Tuyet; Niu, Hengyao; Xue, Xiaoyu; Ira, Grzegorz; Sung, Patrick

Published In Genes Dev, (2017 Mar 01)

Abstract: DNA double-strand break repair by homologous recombination entails nucleolytic resection of the 5' strand at break ends. Dna2, a flap endonuclease with 5'-3' helicase activity, is involved in the resection process. The Dna2 helicase activity has been implicated in Okazaki fragment processing during DNA replication but is thought to be dispensable for DNA end resection. Unexpectedly, we found a requirement for the helicase function of Dna2 in end resection in budding yeast cells lacking exonuclease 1. Biochemical analysis reveals that ATP hydrolysis-fueled translocation of Dna2 on ssDNA facilitates 5' flap cleavage near a single-strand-double strand junction while attenuating 3' flap incision. Accordingly, the ATP hydrolysis-defective dna2-K1080E mutant is less able to generate long products in a reconstituted resection system. Our study thus reveals a previously unrecognized role of the Dna2 translocase activity in DNA break end resection and in the imposition of the 5' strand specificity of end resection.

PubMed ID: 28336516 Exiting the NIEHS site

MeSH Terms: 5' Flanking Region/genetics; Adenosine Triphosphate/metabolism; DNA Breaks, Double-Stranded; DNA End-Joining Repair/genetics; DNA Helicases/genetics; DNA Helicases/metabolism*; DNA Repair/genetics*; Mutation; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism*; Saccharomyces cerevisiae/enzymology*; Saccharomyces cerevisiae/genetics*

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