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

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

Research output: Contribution to journalArticle

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)503-510
Number of pages8
JournalGenes and Development
Volume31
Issue number5
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

Keywords

  • DNA repair
  • Double-strand break
  • End resection
  • Homologous recombination

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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