ArticleThe Journal of biological chemistry2012
Okazaki fragment processing-independent role for human Dna2 enzyme during DNA replication.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 61 citations in OpenAlex.
- Activation of Pol theta-mediated end joining begins during mitotic commitment.bioRxiv : the preprint server for biology · 2026Article
- Multi-omics analysis positions DNA2 at the interface of genome integrity programs and tumor behavior in pan-cancer.Functional & integrative genomics · 2026Article
- The need for speed: drivers and consequences of accelerated replication forks.Communications biology · 2025Review
- Article
- Autophagy induction enhances homologous recombination-associated CRISPR-Cas9 gene editing.Nucleic acids research · 2025Article
- Identification of Brain Cell Type-Specific Therapeutic Targets for Glioma From Genetics.CNS neuroscience & therapeutics · 2024Article
- USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.Nature communications · 2024Article
- FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability.Nucleic acids research · 2023Article
- Inducing multiple nicks promotes interhomolog homologous recombination to correct heterozygous mutations in somatic cells.Nature communications · 2023Article
- Rothmund-Thomson syndrome, a disorder far from solved.Frontiers in aging · 2023Review
- DNA2 mutation causing multisystemic disorder with impaired mitochondrial DNA maintenance.Journal of human genetics · 2022Article
- Review
- Limiting homologous recombination at stalled replication forks is essential for cell viability: DNA2 to the rescue.Current genetics · 2020Review
- Disease-associated DNA2 nuclease-helicase protects cells from lethal chromosome under-replication.Nucleic acids research · 2020Article
- The iron-sulphur cluster in human DNA2 is required for all biochemical activities of DNA2.Communications biology · 2020Article
- CtIP promotes the motor activity of DNA2 to accelerate long-range DNA end resection.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- BLM has Contrary Effects on Repeat-Mediated Deletions, based on the Distance of DNA DSBs to a Repeat and Repeat Divergence.Cell reports · 2020Article
- Multiple roles of DNA2 nuclease/helicase in DNA metabolism, genome stability and human diseases.Nucleic acids research · 2020Review
- TRAF6 mediates human DNA2 polyubiquitination and nuclear localization to maintain nuclear genome integrity.Nucleic acids research · 2019Article
- Biallelic variants in DNA2 cause microcephalic primordial dwarfism.Human mutation · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Dna2 is an essential helicase/nuclease that is postulated to cleave long DNA flaps that escape FEN1 activity during Okazaki fragment (OF) maturation in yeast. We previously demonstrated that the human Dna2 orthologue (hDna2) localizes to the nucleus and contributes to genomic stability. Here we investigated the role hDna2 plays in DNA replication. We show that Dna2 associates with the replisome protein And-1 in a cell cycle-dependent manner. Depletion of hDna2 resulted in S/G(2) phase-specific DNA damage as evidenced by increased γ-H2AX, replication protein A foci, and Chk1 kinase phosphorylation, a readout for activation of the ATR-mediated S phase checkpoint. In addition, we observed reduced origin firing in hDna2-depleted cells consistent with Chk1 activation. We next examined the impact of hDna2 on OF maturation and replication fork progression in human cells. As expected, FEN1 depletion led to a significant reduction in OF maturation. Strikingly, the reduction in OF maturation had no impact on replication fork progression, indicating that fork movement is not tightly coupled to lagging strand maturation. Analysis of hDna2-depleted cells failed to reveal a defect in OF maturation or replication fork progression. Prior work in yeast demonstrated that ectopic expression of FEN1 rescues Dna2 defects. In contrast, we found that FEN1 expression in hDna2-depleted cells failed to rescue genomic instability. These findings suggest that the genomic instability observed in hDna2-depleted cells does not arise from defective OF maturation and that hDna2 plays a role in DNA replication that is distinct from FEN1 and OF maturation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.