ArticleNucleic acids research2015
The Saccharomyces cerevisiae Dna2 can function as a sole nuclease in the processing of Okazaki fragments in DNA replication.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- Rad27/FEN1 prevents accumulation of Okazaki fragments and ribosomal DNA copy number changes.FEBS letters · 2025Article
- RPA and Rad27 limit templated and inverted insertions at DNA breaks.Nucleic acids research · 2025Article
- Proteasome-mediated degradation of long-range nucleases negatively regulates resection of DNA double-strand breaks.iScience · 2024Article
- Rad53 arrests leading and lagging strand DNA synthesis via distinct mechanisms in response to DNA replication stress.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy.Biomolecules · 2022Review
- TheGenes · 2022Article
- Genome-wide and molecular characterization of theFrontiers in genetics · 2022Article
- Distinct RPA domains promote recruitment and the helicase-nuclease activities of Dna2.Nature communications · 2021Article
- The Pif1 helicase is actively inhibited during meiotic recombination which restrains gene conversion tract length.Nucleic acids research · 2021Article
- Review
- Specific Human ATR and ATM Inhibitors Modulate Single Strand DNA Formation inFrontiers in cellular and infection microbiology · 2021Article
- On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability.The Journal of biological chemistry · 2020Review
- Large-scale contractions of Friedreich's ataxia GAA repeats in yeast occur during DNA replication due to their triplex-forming ability.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- RPA and Pif1 cooperate to remove G-rich structures at both leading and lagging strand.Cell stress · 2020Article
- Multiple roles of DNA2 nuclease/helicase in DNA metabolism, genome stability and human diseases.Nucleic acids research · 2020Review
- Plant Organelle Genome Replication.Plants (Basel, Switzerland) · 2019Review
- Human DNA polymerase delta requires an iron-sulfur cluster for high-fidelity DNA synthesis.Life science alliance · 2019Article
- Processing of eukaryotic Okazaki fragments by redundant nucleases can be uncoupled from ongoing DNA replication in vivo.Nucleic acids research · 2019Article
- Review
- Sumoylation regulates the stability and nuclease activity ofCommunications biology · 2019Article
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2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During DNA replication, synthesis of the lagging strand occurs in stretches termed Okazaki fragments. Before adjacent fragments are ligated, any flaps resulting from the displacement of the 5' DNA end of the Okazaki fragment must be cleaved. Previously, Dna2 was implicated to function upstream of flap endonuclease 1 (Fen1 or Rad27) in the processing of long flaps bound by the replication protein A (RPA). Here we show that Dna2 efficiently cleaves long DNA flaps exactly at or directly adjacent to the base. A fraction of the flaps cleaved by Dna2 can be immediately ligated. When coupled with DNA replication, the flap processing activity of Dna2 leads to a nearly complete Okazaki fragment maturation at sub-nanomolar Dna2 concentrations. Our results indicate that a subsequent nucleolytic activity of Fen1 is not required in most cases. In contrast Dna2 is completely incapable to cleave short flaps. We show that also Dna2, like Fen1, interacts with proliferating cell nuclear antigen (PCNA). We propose a model where Dna2 alone is responsible for cleaving of RPA-bound long flaps, while Fen1 or exonuclease 1 (Exo1) cleave short flaps. Our results argue that Dna2 can function in a separate, rather than in a Fen1-dependent pathway.
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