Affinage

DNA2

DNA replication ATP-dependent helicase/nuclease DNA2 · UniProt P51530

Length
1060 aa
Mass
120.4 kDa
Annotated
2026-06-09
100 papers in source corpus 52 papers cited in narrative 51 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNA2 is a bifunctional, ATP-dependent enzyme that combines a single-stranded DNA endonuclease with a 5'→3' helicase/translocase motor in one polypeptide to process DNA intermediates that arise during replication, recombinational repair, and telomere maintenance, thereby safeguarding genome integrity (PMID:7592912, PMID:9756935, PMID:16595800). The enzyme threads ssDNA through a long internal tunnel to its nuclease active site (PMID:26491943), and its nuclease, ATPase, and helicase activities are mechanistically coupled — a Walker A mutation abolishes all three (PMID:9756935) and an iron-sulfur cluster spanning the nuclease site is required for both nuclease and ATPase function (PMID:22684504) — with the nuclease normally suppressing the latent helicase by cleaving the flap substrate required for helicase loading (PMID:23671118, PMID:27612385). In Okazaki fragment maturation DNA2 acts specifically on long 5'-flaps that have become coated by RPA, shortening or precisely cleaving them at the duplex junction so that FEN1 or ligase can complete maturation; short flaps are handled by FEN1 alone, and the two nucleases act in an ordered, partly redundant pathway (PMID:12424238, PMID:19605347, PMID:26175049, PMID:17038322). In DNA double-strand break repair, DNA2 carries out long-range 5'-strand resection in obligate partnership with a RecQ helicase (yeast Sgs1; human BLM and WRN) and RPA, where the helicase unwinds the duplex and RPA enforces 5'→3' polarity by directing DNA2 to degrade only the 5'-terminated strand (PMID:18805091, PMID:20811461, PMID:21325134, PMID:25122754); a structurally defined, mutually exclusive second DNA2–RPA contact displaces RPA from the 5' end to establish this polarity (PMID:26491943, PMID:34764291). DNA2 also recognizes and cleaves G-quadruplex DNA and reversed replication forks, restraining fork reversal and promoting fork restart, and localizes to both mitochondria — where it cooperates with Pol gamma and FEN1 in mtDNA replication and long-patch base excision repair — and the nucleus, where it maintains telomeres and chromosomal stability (PMID:18593712, PMID:22682245, PMID:25733713, PMID:18995831, PMID:23604072, PMID:19487465). Its activity is tightly controlled: Cdk1 phosphorylation promotes DSB recruitment (PMID:21841787), Cds1/Chk2 phosphorylation regulates fork association (PMID:22682245), TRAF6-mediated K63 ubiquitination drives nuclear localization (PMID:31216032), p300 acetylation stimulates its activities while inhibiting FEN1 (PMID:20019387), CtIP stimulates its motor activity in a manner blocked by PLK1 phosphorylation of CtIP (PMID:32241893, PMID:36746606), and FANCD2 and RAD51 directly inhibit it to protect stalled forks (PMID:37526271). Biallelic DNA2 mutations that impair its catalytic activities cause adult-onset mitochondrial myopathy with multiple mtDNA deletions (PMID:23352259).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1995 High

    Establishing that DNA2 is an essential helicase needed for replication defined it as a core replication factor rather than an accessory protein.

    Evidence In vitro helicase assay on forked substrates plus in vivo domain-deletion complementation in yeast

    PMID:7592912

    Open questions at the time
    • Did not reveal the nuclease activity
    • N-terminal domain function undefined
  2. 1998 High

    Discovery of an intrinsic ssDNA endonuclease in the same polypeptide as the helicase, with all activities lost by a single ATP-site mutation, established DNA2 as a single bifunctional nuclease-helicase.

    Evidence Reconstituted nuclease/ATPase assays with Walker A mutagenesis of purified Dna2

    PMID:9756935

    Open questions at the time
    • Physiological substrate not yet defined
    • Coupling mechanism between activities unknown
  3. 2000 High

    Separation-of-function mutants showed the nuclease (not helicase alone) is essential for viability and primer removal, ranking the two activities and tying DNA2 to Okazaki fragment processing.

    Evidence Nuclease-dead and helicase-directionality assays plus in vivo complementation in yeast

    PMID:10748138 PMID:10908349 PMID:10984490

    Open questions at the time
    • Why long flaps specifically require DNA2 not yet defined
    • Role of RPA not yet established
  4. 2002 High

    Reconstituted Okazaki maturation defined DNA2's niche: it processes specifically the long RPA-bound flaps that FEN1 cannot handle, with the helicase aiding removal of secondary structure.

    Evidence Fully reconstituted yeast Okazaki maturation with Pol delta, PCNA, FEN1, Dna2, ligase, RPA; separation-of-function mutant mixing

    PMID:12004053 PMID:12424238

    Open questions at the time
    • How DNA2 and FEN1 are ordered on the same flap unresolved
    • RPA interaction interface not mapped
  5. 2003 High

    Mapping a bimodal RPA interaction that both recruits DNA2 and stimulates its nuclease, and is genetically essential, established RPA as the central regulator of DNA2 function.

    Evidence Allele-specific synthetic lethality, Co-IP, and RPA domain-mutant stimulation assays

    PMID:12799426

    Open questions at the time
    • Structural basis of recruitment-vs-stimulation duality unresolved at this stage
  6. 2006 High

    Comprehensive biochemistry of human DNA2 confirmed conservation of ATPase, helicase, and dual-polarity flap nuclease activities, extending the yeast model to humans.

    Evidence Purified recombinant human DNA2; ATPase, helicase, nuclease assays on defined flap and fork substrates

    PMID:16595799 PMID:16595800

    Open questions at the time
    • Cellular localization and in vivo roles not addressed here
    • G4 and resection functions not yet tested
  7. 2006 Medium

    Demonstrating that DNA2 binds and cleaves G-quadruplex DNA, and that FEN1 actively displaces DNA2 from flaps, defined both an alternative substrate class and the ordered handoff between the two nucleases.

    Evidence G4 binding/helicase/nuclease assays with RPA titration; gel-shift displacement and cleavage competition with nuclease-dead Dna2

    PMID:17038322 PMID:18593712

    Open questions at the time
    • In vivo significance of G4 processing not yet shown
    • Structural basis of FEN1 displacement unknown
  8. 2008 High

    Defining DNA2 as a long-range 5'-resection nuclease acting with Sgs1/BLM at DSBs, and localizing human DNA2 to mitochondria with Pol gamma, expanded its role from replication into both DSB repair and mtDNA maintenance.

    Evidence In vivo DSB resection assays and deletion epistasis in yeast; subcellular fractionation, Pol gamma Co-IP, and mitochondrial LP-BER assays for human DNA2

    PMID:18799459 PMID:18805091 PMID:18995831

    Open questions at the time
    • Nuclear vs mitochondrial partitioning mechanism in humans unresolved
    • How RPA enforces 5' polarity not yet reconstituted
  9. 2010 High

    Biochemical reconstitution of a minimal Sgs1/BLM–DNA2–RPA resection machine established the division of labor: helicase unwinds, RPA enforces 5'→3' polarity, and DNA2 degrades the 5' strand.

    Evidence Reconstituted DNA end resection with purified Sgs1/BLM, DNA2, RPA, MRX/MRN, Top3-Rmi1

    PMID:20811461 PMID:20834227 PMID:21325134

    Open questions at the time
    • Structural basis of polarity enforcement still inferred
    • Recruitment to ends in vivo only partly defined
  10. 2011 High

    Identifying Cdk1 phosphorylation of DNA2 that promotes DSB recruitment connected cell-cycle control to resection commitment.

    Evidence Phospho-site mutagenesis with ChIP and resection assays in yeast

    PMID:21841787

    Open questions at the time
    • Direct binding partner mediating phospho-dependent recruitment unidentified
  11. 2012 High

    Discovery of Cds1/Chk2 phosphorylation regulating fork association, an Fe-S cluster coupling the catalytic modules, and a checkpoint-activating N-terminal region positioned DNA2 as both a fork-protective nuclease and a signaling input.

    Evidence Kinase assays, chromatin fractionation, fork-reversal and Mec1 activation assays; Fe-S cysteine mutagenesis

    PMID:22682245 PMID:22684504 PMID:23355394

    Open questions at the time
    • How the Fe-S cluster mechanically couples nuclease and helicase unresolved
    • In vivo checkpoint contribution of DNA2 vs redundant activators incompletely separated
  12. 2013 High

    Showing that the nuclease suppresses the helicase by consuming its loading substrate, and that DNA2 protects telomeres by cleaving G4 in vivo, clarified the internal regulatory logic and a physiological G4 function with cancer relevance.

    Evidence Single-molecule unwinding with nuclease-dead Dna2; in vitro G4 cleavage plus mouse knockout cytogenetics and tumor analysis; patient-mutation biochemistry

    PMID:23352259 PMID:23604072 PMID:23671118

    Open questions at the time
    • Trigger that relieves nuclease suppression to unleash helicase in vivo unknown
    • Mechanistic link from DNA2 loss to aneuploidy not fully resolved
  13. 2014 High

    Confirming that human WRN and BLM act epistatically and physically with DNA2 in long-range resection generalized the helicase-nuclease resection module across human RecQ helicases.

    Evidence Co-IP, reconstituted resection, and siRNA epistasis in human cells

    PMID:25122754 PMID:25200081

    Open questions at the time
    • When WRN vs BLM is selected as the DNA2 partner unknown
  14. 2015 High

    The crystal structure of intact Dna2 bound to ssDNA, revealing a threading tunnel and a second mutually exclusive Dna2-RPA contact, gave the structural mechanism for 5' end recognition and resection polarity, while fiber/iPOND work defined DNA2-WRN degradation of reversed forks.

    Evidence 2.3 Å X-ray structure with structure-guided mutagenesis; DNA fiber and iPOND analyses with nuclease depletions; reconstituted sole-nuclease Okazaki maturation

    PMID:25733713 PMID:26175049 PMID:26491943

    Open questions at the time
    • Conformational dynamics during translocation not captured
    • Regulation distinguishing fork protection from degradation incomplete
  15. 2016 High

    Demonstrating that human DNA2 is itself a processive kilobase helicase, normally masked by its nuclease, and integrates with BLM/WRN as a heterodimeric motor, redefined DNA2 as a genuine dual-motor enzyme.

    Evidence Single-molecule and bulk helicase assays with nuclease-dead variant and BLM/WRN co-reconstitution

    PMID:27612385

    Open questions at the time
    • Physiological contexts where the unleashed helicase operates in vivo unclear
  16. 2017 High

    Establishing that the DNA2 motor/translocase activity drives degradation of RPA-coated ssDNA and contributes to 5' specificity and resection speed, and that CtIP stimulates this motor, integrated the helicase into the resection mechanism and added a stimulatory partner.

    Evidence Single-molecule and ensemble ssDNA-degradation assays with K1080E mutant; in vivo resection in helicase-dead yeast; CtIP phospho/domain-mapping

    PMID:28336515 PMID:28336516 PMID:32241893

    Open questions at the time
    • How CtIP stimulation is restricted to specific cell-cycle windows not yet defined here
  17. 2019 Medium

    Identifying TRAF6-mediated K63 ubiquitination as the driver of DNA2 nuclear localization, and single-molecule evidence that DNA2 triggers processive Sgs1 translocation, linked post-translational control of DNA2 trafficking to activation of the resection motor.

    Evidence Co-IP, ubiquitination and nuclear fractionation with functional resection/HDR reporters; single-molecule imaging of Sgs1-Dna2-Top3-Rmi1-RPA

    PMID:30850524 PMID:31216032

    Open questions at the time
    • TRAF6-DNA2 axis from single lab
    • Signal that triggers TRAF6-mediated modification unknown
  18. 2020 High

    Showing PCNA ubiquitination restrains DNA2-dependent degradation of nascent DNA at stalled forks tied DNA2 fork activity to Okazaki maturation defects and PCNA dynamics.

    Evidence CRISPR PCNA-ubiquitination mutant cells, DNA fiber assays, and nuclease depletions

    PMID:32358495

    Open questions at the time
    • Direct PCNA-DNA2 regulatory interaction at forks not fully resolved
  19. 2021 High

    Separating the RPA domains that recruit DNA2 from those that stimulate its nuclease versus motor activities resolved RPA as a multi-output regulator acting through distinct surfaces.

    Evidence Structure-guided RPA mutagenesis with single-molecule and ensemble resection assays

    PMID:34764291

    Open questions at the time
    • How these RPA outputs are coordinated temporally during resection unresolved
  20. 2023 High

    Defining FANCD2 and RAD51 as direct DNA2 inhibitors, and PLK1 phosphorylation of CtIP as a cell-cycle switch that withdraws CtIP stimulation of DNA2, established the negative-regulatory layer that limits resection and protects forks.

    Evidence In vitro nuclease inhibition with purified FANCD2/RAD51 and domain mapping; structural-model-guided CtIP separation-of-function mutant with kinase and cellular assays

    PMID:36746606 PMID:37526271

    Open questions at the time
    • Integration of multiple inhibitory inputs at a single fork not modeled
    • In vivo balance between stimulation and inhibition incompletely defined
  21. 2025 Medium

    Distinguishing DNA2-WRN/BLM 5' gap resection (MRN-CtIP independent) from MRN 3'→5' gap resection revealed a context-specific role of DNA2 at ssDNA gaps with implications for PARP-inhibitor sensitivity in BRCA1-deficient cells.

    Evidence Single-molecule DNA fiber analysis, EM, and reconstitution with ssDNA gap substrates

    PMID:40127955

    Open questions at the time
    • Single study at gaps
    • How gap-resection is regulated vs DSB resection unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many regulatory inputs (phosphorylation, acetylation, ubiquitination, RPA, CtIP, FANCD2/RAD51) are integrated in real time to switch DNA2 between Okazaki processing, resection, and fork protection at a given genomic location remains unresolved.
  • No unified in vivo model of competing activators and inhibitors at a single substrate
  • Spatial/temporal control of the latent helicase vs dominant nuclease unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 5 GO:0140097 catalytic activity, acting on DNA 5 GO:0140098 catalytic activity, acting on RNA 5 GO:0140657 ATP-dependent activity 5 GO:0003677 DNA binding 3
Localization
GO:0005739 mitochondrion 3 GO:0005634 nucleus 2 GO:0005694 chromosome 2
Pathway
R-HSA-69306 DNA Replication 4 R-HSA-73894 DNA Repair 4 R-HSA-1640170 Cell Cycle 3 R-HSA-8953854 Metabolism of RNA 3
Partners
BLMCTIPFANCD2FEN1PCNARPA1SGS1WRN

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 DNA2 encodes a 172-kDa protein with an intrinsic 3'-to-5' DNA helicase activity specific for forked substrates; the helicase domain is required in vivo for DNA replication, and the N-terminal half (no similarity to known helicases) is also essential for replication. In vitro helicase assay with purified Dna2p; in vivo complementation with domain-deletion mutants in yeast The Journal of biological chemistry High 7592912
1997 Yeast Dna2 helicase physically interacts with yeast FEN-1 (Rad27) nuclease; the two proteins co-immunopurify, show synthetic lethality when both are mutated, and overexpression of either suppresses defects of the other, placing Dna2 and FEN-1 in the same Okazaki fragment processing pathway. Co-immunoprecipitation; genetic suppression (overexpression rescue); synthetic lethality analysis Molecular and cellular biology High 9121462
1998 Saccharomyces cerevisiae Dna2 possesses an intrinsic ssDNA-specific endonuclease activity and can degrade duplex DNA in an ATP-dependent manner; ATP hydrolysis is required for the duplex-DNA nuclease activity; a Walker A box mutation simultaneously abolishes ATPase, helicase, and ATP-dependent nuclease, indicating all activities reside in the same polypeptide. In vitro nuclease and ATPase assays with purified recombinant Dna2; site-directed mutagenesis of ATP-binding motif The Journal of biological chemistry High 9756935
1999 Dna2 helicase activity is not essential for viability but is required for optimal DNA repair and for tolerating loss of Ctf4; genetic interactions with POL1 (DNA Pol alpha subunit) and CTF4 place Dna2 in a lagging-strand synthesis/repair process involving Pol alpha. Separation-of-function mutagenesis; synthetic lethality with ctf4Δ; genetic epistasis with RAD9 checkpoint Genetics Medium 10101169
2000 Dna2 helicase translocates 5'→3' and preferentially uses DNA with free ends; its endonuclease is markedly stimulated by an RNA segment at the 5'-end of ssDNA and cleaves within the DNA to ensure complete primer removal; these properties support a direct role in Okazaki fragment RNA primer removal. In vitro helicase directionality assays; endonuclease assays with RNA-DNA hybrid substrates; purified recombinant Dna2 The Journal of biological chemistry High 10984490
2000 The nuclease activity of Dna2, but not helicase activity alone, is essential for cell viability; nuclease-dead point mutations (D657A, related) abolish endonuclease but retain helicase, and cells expressing only nuclease-dead Dna2 cannot grow; nuclease is required for Okazaki fragment processing in vivo. Site-directed mutagenesis; in vivo complementation assays; purified mutant protein biochemical characterization The Journal of biological chemistry High 10748138 10908349
2000 Fission yeast dna2 mutants arrest at late S-phase; overexpression of genes encoding Pol delta subunits, DNA ligase I (Cdc17), and Fen-1 (Rad2) suppress dna2 temperature sensitivity; two-hybrid and biochemical interaction data show Dna2 forms a complex with these Okazaki fragment elongation/maturation factors, placing it as a central coordinator of that process. Genetic suppression; two-hybrid interaction; cell cycle analysis Genetics Medium 10880469
2001 Dna2 has a tripartite domain structure: an N-terminal 45 kDa regulatory domain, and two catalytic core fragments (~58 and ~60 kDa); removal of the N-terminal domain increases ATPase and endonuclease activities 3–8-fold; the N-terminal domain interacts physically with the central region between the two catalytic domains and is essential for normal in vivo function. Limited proteolysis; biochemical activity assays of fragments; in vivo growth complementation; hydrodynamic analysis Nucleic acids research Medium 11452032
2002 In reconstituted Okazaki fragment maturation, Dna2 is required specifically to process long 5'-flaps to which RPA can bind, whereas short flaps and RNA primers are efficiently processed by FEN1 alone; Dna2 does not affect FEN1-mediated nick translation on short substrates. In vitro reconstituted Okazaki fragment maturation with purified yeast proteins (Pol delta, PCNA, FEN1, Dna2, ligase, RPA) The Journal of biological chemistry High 12424238
2002 Dna2 helicase activity facilitates removal of secondary structures in 5'-flap DNA by its intrinsic endonuclease; mixing helicase-only (D657A) and nuclease-only (K1080E) Dna2 mutants showed that the helicase promotes translocation-coupled cleavage, with RPA further aiding secondary structure removal. In vitro endonuclease/helicase assays with separation-of-function mutants and reconstituted flap substrates The Journal of biological chemistry High 12004053
2003 RPA (via its large subunit Rpa1) physically interacts with Dna2 through a bimodal interaction: a C-terminal interaction mediates recruitment, and an N-terminal domain of Rpa1 maximally stimulates Dna2 endonuclease activity; this interaction is genetically essential (synthetic lethality with rfa1 alleles). Allele-specific synthetic lethality; co-immunoprecipitation; in vitro endonuclease stimulation assays with RPA domain mutants Nucleic acids research High 12799426
2003 Human BLM helicase physically interacts with both S. cerevisiae Dna2 and FEN1 (co-immunoprecipitation from yeast extracts) and suppresses the temperature-sensitive growth defect and DNA damage sensitivity of dna2-1 mutants, suggesting BLM participates in the same Okazaki fragment maturation/repair steps as Dna2 and FEN1. Co-immunoprecipitation; genetic suppression of yeast dna2 mutants by human BLM Proceedings of the National Academy of Sciences of the United States of America Medium 12826610
2004 Fission yeast Dna2 is required for generation of telomeric G-rich single-strand overhangs; Dna2 binds telomere DNA (ChIP), and dna2 mutants show reduced G-overhang and telomere shortening, demonstrating a role distinct from DSB end processing. Chromatin immunoprecipitation; telomere G-overhang assay; genetic analysis of double mutants Molecular and cellular biology Medium 15485922
2006 Pif1 helicase functions epistatically with Dna2 in Okazaki fragment processing; deletion of PIF1 suppresses lethality of dna2Δ, and further deletion of POL32 (Pol delta subunit) suppresses additional defects, consistent with a model where Pif1/Pol delta strand displacement generates long flaps requiring Dna2. Genetic epistasis; synthetic lethality; suppression analysis in yeast Molecular and cellular biology Medium 16537895
2006 Human DNA2 (hDna2) has ssDNA-dependent ATPase and DNA helicase activity, 5'→3' nuclease activity preferring 5'-flaps adjacent to duplex DNA (stimulated by RPA), and strong 3'→5' nuclease activity on fork structures; both nuclease polarities are suppressed by steric hindrance at their respective strand ends. Biochemical characterization of purified recombinant hDna2; ATPase, helicase, and nuclease assays with defined substrates Nucleic acids research High 16595800
2006 Purified human Dna2 has intrinsic endonuclease and DNA-dependent ATPase activities; on forked structures bearing both 5' and 3' ssDNA tails, hDna2 cleaves both with equal efficiency, suggesting a role in processing equilibrating flaps during Okazaki fragment maturation. Purification of recombinant hDna2 from transfected human cells; endonuclease and ATPase assays with defined substrates Nucleic acids research High 16595799
2006 FEN1 actively disengages Dna2 from flap substrates: FEN1 displaces pre-bound Dna2 (including nuclease-inactive Dna2) to allow FEN1 to cleave, explaining the ordered sequential action of Dna2 then FEN1 in Okazaki fragment processing. Gel shift assays; cleavage competition assays with wild-type and nuclease-dead Dna2 mutant The Journal of biological chemistry Medium 17038322
2006 Both yeast and human Dna2 possess strand annealing and ATP-independent strand exchange activities on short duplexes; these activities are independent of ATPase/helicase and nuclease activities (mutations eliminating either do not inhibit annealing/exchange); ATP inhibits strand exchange. In vitro strand annealing and exchange assays with separation-of-function mutant proteins The Journal of biological chemistry Medium 17032657
2008 Human DNA2 localizes to mitochondria (not nuclei) due to absence of a nuclear localization signal; it interacts with mitochondrial DNA polymerase gamma, stimulates its activity, and together with FEN1 processes 5'-flap intermediates in mitochondrial DNA replication and long-patch base excision repair; depletion reduces mitochondrial RNA primer removal and LP-BER efficiency. Subcellular fractionation; immunofluorescence; co-immunoprecipitation with Pol gamma; mitochondrial extract LP-BER assay; siRNA depletion Molecular cell High 18995831
2008 Yeast and human Dna2 bind G-quadruplex (G4) DNA with ~25-fold higher affinity than linear ssDNA of the same sequence; Dna2 helicase efficiently unwinds G4 DNA; Dna2 nuclease activity on G4 DNA is attenuated but is restored by RPA, which simultaneously inhibits Dna2's 3'→5' nuclease on G4 substrates. In vitro binding assays; helicase and nuclease assays with G4 substrates; RPA titration experiments The Journal of biological chemistry High 18593712
2008 In yeast, the Mre11-Rad50-Xrs2 (MRX) complex with Sae2 initiates 5'-strand resection (~few hundred nt), while Sgs1 and Dna2 perform long-range 5'-strand resection; deletion of SGS1 or DNA2 reduces long-range resection and DSB repair by single-strand annealing; Exo1 provides an alternative long-range resection pathway. In vivo resection assay at inducible DSBs (Southern blot/quantitative PCR); genetic deletion analysis in yeast Cell High 18805091
2008 Dna2 binding alone (without cleavage) dissociates RPA from flap-bound ssDNA; this dissociation is specific to genuine flap substrates and enables subsequent FEN1 cleavage of RPA-coated flaps; coordinated RPA displacement by Dna2 prevents flap re-folding. Nuclease-defective Dna2 mutant binding assays; RPA dissociation measured by gel shift; reconstituted flap processing The Journal of biological chemistry Medium 18799459
2009 Human DNA2 is present in both the nucleus and mitochondria; in the nucleus it co-localizes with mitochondrial nucleoid-associated proteins upon replication stress; depletion causes aneuploidy and internuclear chromatin bridges, indicating a nuclear role in genomic DNA stability independent of mitochondria. Immunofluorescence; biochemical fractionation; siRNA depletion; cell cycle/chromosome analysis Molecular and cellular biology High 19487465
2009 Pif1 helicase promotes DNA Pol delta to displace strands long enough to bind RPA, creating substrates for Dna2; in a fully reconstituted Okazaki fragment processing system, RPA-coated long flaps inhibit ligation unless Dna2 is present to shorten them, demonstrating the functional necessity of the two-nuclease (Dna2 + FEN1) pathway for long flap processing. Reconstituted in vitro Okazaki fragment processing with purified yeast proteins; ligation efficiency assay The Journal of biological chemistry High 19605347
2009 p300 acetylates Dna2, stimulating its 5'→3' endonuclease, 5'→3' helicase, and DNA-dependent ATPase activities, and increasing Dna2's DNA-binding affinity; simultaneously p300 acetylates FEN1 and inhibits it, thereby promoting longer flap intermediates that are directed to Dna2 processing. In vitro acetylation assay with p300; endonuclease, helicase, ATPase, and DNA-binding assays with acetylated proteins The Journal of biological chemistry Medium 20019387
2010 Biochemical reconstitution with purified Dna2, Sgs1, and RPA establishes a minimal protein complex capable of DNA end resection in vitro; Sgs1 helicase unwinds DNA to generate an intermediate digested by Dna2 nuclease; RPA stimulates Sgs1 unwinding in a species-specific manner and directs Dna2 to degrade only the 5'-strand while inhibiting 3'→5' degradation. Top3-Rmi1 and MRX stimulate resection by forming complexes with Sgs1 to enhance unwinding. In vitro reconstituted DNA end resection with purified proteins; nuclease polarity assays with RPA; protein interaction studies Nature High 20811461
2010 MRX recruits Dna2 nuclease to DSB ends in vivo; MRX and Ku regulate the association of Dna2 and Exo1 with DSBs; in vitro, Ku and MRX have opposing effects on Exo1 nuclease activity; Mre11 nuclease activity is dispensable for loading Dna2 but is essential for resection when long-range resection enzymes are absent. ChIP at DSBs in yeast; in vitro nuclease assays with purified proteins; genetic epistasis The EMBO journal High 20834227
2011 Human BLM and DNA2 physically interact and together reconstitute DNA end resection in vitro in a reaction requiring BLM helicase activity and DNA2 nuclease activity; RPA is essential for both BLM-mediated unwinding and for enforcing 5'→3' resection polarity by DNA2; MRN accelerates resection by recruiting BLM to DNA ends. Biochemical reconstitution of human resection with purified BLM, DNA2, RPA, MRN, EXO1; co-immunoprecipitation; domain-specific mutant analysis Genes & development High 21325134
2011 Cdk1 phosphorylates Dna2 at Thr4, Ser17, and Ser237 in yeast; these phosphorylations promote Dna2 recruitment to DSBs and stimulate resection; phospho-deficient dna2T4A S17A S237A mutants show reduced DSB recruitment and resection, with remaining resection activity dependent on Exo1. Phospho-site mutagenesis; ChIP at induced DSBs; resection assays in phospho-mutant yeast strains Nature structural & molecular biology High 21841787
2012 The intra-S phase checkpoint effector kinase Cds1 (Chk2) phosphorylates Dna2 at S220 in fission yeast; this phosphorylation regulates Dna2 association with stalled replication forks in chromatin; Dna2-S220 phosphorylation and Dna2 nuclease activity are required to prevent fork reversal; Dna2 cleaves regressed leading and lagging strand substrates on model replication forks in vitro. Kinase phosphorylation assay; chromatin fractionation; in vivo and in vitro fork reversal assays; nuclease assay on model fork substrates Cell High 22682245
2012 Dna2 N-terminal region (residues W128 and Y130) stimulates Mec1 (ATR ortholog) kinase activity during S phase to initiate the replication checkpoint; Dna2 is partially redundant with 9-1-1 and Dpb11 as Mec1 activators; a triple mutant eliminating all three activators abrogates the checkpoint. In vitro Mec1 kinase assay; in vivo checkpoint assay with dna2 N-terminal point mutants; genetic epistasis with checkpoint mutants Genes & development High 23355394
2013 Saccharomyces cerevisiae Dna2 nuclease inhibits its own helicase by cleaving the 5'-flap substrate required for helicase loading; mutational inactivation of Dna2 nuclease unleashes vigorous DNA unwinding comparable to the most potent eukaryotic helicases, demonstrating that the nuclease controls the helicase activity. Nuclease-deficient Dna2 mutant helicase assays; single-molecule and ensemble unwinding experiments Proceedings of the National Academy of Sciences of the United States of America High 23671118
2013 Mammalian DNA2 recognizes and cleaves telomeric G-quadruplex structures in vitro; DNA2-deficient mouse cells show elevated fragile telomeres, sister telomere associations, and telomere DNA damage, phenotypes enhanced by G4 stabilizers; DNA2-deficient mice develop aneuploidy-associated cancers. In vitro G4 cleavage assay; genetic knockout in mouse cells; cytogenetic analysis; in vivo tumor analysis The EMBO journal High 23604072
2013 Mutations in human DNA2 identified in adult-onset mitochondrial myopathy patients cause severe impairment of nuclease, helicase, and ATPase activities in vitro, and are associated with multiple mtDNA deletions, implicating DNA2 in mitochondrial DNA maintenance and LP-BER. Biochemical analysis of purified mutant DNA2 proteins; ATPase, helicase, and nuclease assays; exome sequencing of patient cohort American journal of human genetics Medium 23352259
2014 WRN and BLM helicases act epistatically with DNA2 in long-range DSB end resection in human cells; WRN physically interacts with DNA2 and coordinates enzymatic activities with DNA2 to mediate 5'→3' resection in a RPA-dependent manner in vitro; BLM promotes resection as part of the BLM-TOPOIIIα-RMI1-RMI2 complex. Co-immunoprecipitation; in vitro reconstituted resection assay; siRNA epistasis in human cells; resection measurement at DSBs The Journal of biological chemistry High 25122754
2014 Topo IIIα stimulates BLM-mediated DNA unwinding in a manner potentiated by RMI1-RMI2; the processivity of resection depends on the Topo IIIα-RMI1-RMI2 complex; RPA contributes to 5'→3' resection polarity; DNA2 stimulates the helicase activity of BLM. Reconstituted resection assay with purified human proteins; DNA unwinding assays with domain mutants Nucleic acids research Medium 25200081
2015 The 2.3 Å crystal structure of intact mouse Dna2 bound to 15-nt ssDNA reveals a long narrow tunnel through which ssDNA threads to reach the nuclease active site; the helicase domain is required for DNA binding but not threading; a flexibly tethered Dna2-RPA interaction recruits Dna2 to RPA-coated DNA, while a second Dna2-RPA interaction (mutually exclusive with RPA-DNA) displaces RPA from the 5' end of ssDNA only, explaining 5'→3' resection polarity. X-ray crystallography (2.3 Å); structure-guided mutagenesis; biochemical functional validation of RPA-Dna2 interactions eLife High 26491943
2015 Human DNA2 and WRN nuclease/ATPase activities functionally interact to degrade reversed replication forks with 5'→3' polarity and promote replication restart; RECQ1 limits DNA2 activity by preventing extensive nascent strand degradation; EXO1, MRE11, and CtIP are NOT involved in this mechanism; RAD51 depletion antagonizes it by preventing reversed fork formation. DNA fiber assay; siRNA knockdown of multiple nucleases; iPOND; in vivo replication fork analysis The Journal of cell biology High 25733713
2015 Dna2 can function as a sole nuclease for Okazaki fragment maturation in vitro: it cleaves long RPA-bound flaps exactly at or adjacent to the base, enabling direct ligation; Dna2 also interacts with PCNA. Short flaps cannot be cleaved by Dna2, requiring FEN1 or Exo1. Reconstituted in vitro Okazaki fragment maturation; ligation assay; Dna2-PCNA interaction assay Nucleic acids research High 26175049
2012 An iron-sulfur (Fe-S) cluster domain in yeast Dna2, spanning the nuclease active site, is essential for nuclease activity; mutation of Fe-S cluster coordinating cysteines also impairs ATPase activity and alters DNA-binding mode, demonstrating coupling between the nuclease and helicase modules through this structural element. Site-directed mutagenesis of Fe-S cluster cysteines; in vitro nuclease and ATPase assays; in vivo complementation Nucleic acids research High 22684504
2016 Human DNA2 is a processive helicase capable of unwinding kilobases of dsDNA; the nuclease activity prevents engagement of the helicase by competing for the same substrate (nuclease-deficient variant shows prominent unwinding); the hDNA2 helicase functionally integrates with BLM or WRN to form a heterodimeric motor that promotes dsDNA degradation. Bulk and single-molecule helicase assays; nuclease-deficient variant analysis; BLM/WRN co-reconstitution assays eLife High 27612385
2017 CtIP dramatically stimulates the ATP hydrolysis-driven motor (translocase) activity of DNA2, thereby promoting degradation of RPA-coated ssDNA by DNA2 in long-range resection; this stimulation requires CtIP phosphorylation; the CtIP domain stimulating DNA2 maps to the central region absent in lower eukaryotes and is fully separable from the MRN-stimulating domain. Ensemble and single-molecule biochemistry; CtIP phospho-mutant analysis; domain-deletion mapping; reconstituted long-range resection assay Proceedings of the National Academy of Sciences of the United States of America High 32241893
2017 The motor (helicase/translocase) activity of both yeast and human DNA2 promotes efficient degradation of long ssDNA stretches, particularly when RPA is present; this ssDNA translocase function contributes to resection speed in vivo; helicase-deficient dna2-K1080E cells display reduced resection speed at HO-induced DSBs. In vitro ssDNA degradation assays; single-molecule assays; in vivo DSB resection measurement in helicase-dead mutant yeast Genes & development High 28336515
2017 Dna2 helicase (translocase) activity facilitates 5'-flap cleavage near the ssDNA-dsDNA junction while attenuating 3'-flap incision; ATP hydrolysis-defective dna2-K1080E produces fewer long resection products in reconstituted systems, demonstrating that the translocase activity contributes to the 5'-strand specificity of end resection. Reconstituted resection system; in vitro nuclease polarity assays with ATP-hydrolysis mutant; in vivo epistasis (exo1Δ dna2-K1080E double mutant) Genes & development High 28336516
2019 E3 ligase TRAF6 binds hDNA2 and mediates K63-linked polyubiquitination of hDNA2, increasing its stability and promoting its nuclear localization; inhibiting TRAF6-mediated ubiquitination abolishes nuclear hDNA2, impairing DSB end resection and homology-directed repair. Co-immunoprecipitation; ubiquitination assay; nuclear fractionation; siRNA/inhibitor experiments; resection and HDR reporter assays Nucleic acids research Medium 31216032
2019 Using single-molecule imaging, addition of Dna2 to Sgs1 at DNA ends triggers processive Sgs1 translocation; DNA resection only occurs when RPA is also present; the Sgs1-Dna2-Top3-Rmi1-RPA ensemble can disrupt nucleosomes, and Sgs1 itself possesses nucleosome remodeling activity. Single-molecule fluorescence imaging of DNA end resection; nucleosome disruption assay; reconstituted multi-protein system Proceedings of the National Academy of Sciences of the United States of America High 30850524
2020 Loss of PCNA ubiquitination results in DNA2-dependent (but MRE11-independent) nucleolytic degradation of nascent DNA at stalled replication forks; this is linked to defective Okazaki fragment maturation that impairs PCNA unloading by ATAD5 and nucleosome deposition by CAF-1, identifying PCNA ubiquitination as a regulator of DNA2 activity at forks. CRISPR/Cas9 PCNA ubiquitination mutant cells; DNA fiber assay; siRNA depletion of DNA2 and MRE11; chromatin fractionation Nature communications High 32358495
2021 Different domains of RPA large subunit Rfa1 differentially regulate Dna2: a helix in the Rfa1 N-terminal domain specifically promotes Dna2 nuclease activity (independent of recruitment), while residues on the outside of the Rfa1-A OB-fold promote Dna2 motor activity; Dna2 recruitment to ssDNA is separable from stimulation of its catalytic activities. Single-molecule and ensemble biochemistry; structure-guided mutagenesis of RPA; reconstituted resection assays with separation-of-function RPA mutants Nature communications High 34764291
2023 FANCD2 directly inhibits DNA2 nuclease activity by binding to DNA2 via its N-terminal domain, preventing excessive resection at stalled forks; independently, FANCD2 stabilizes RAD51 filaments to inhibit DNA2, MRE11, and EXO1; RAD51 also directly inhibits DNA2. In vitro nuclease inhibition assay with purified FANCD2 and RAD51; domain-mapping experiments; fork protection assays Nucleic acids research High 37526271
2023 PLK1 phosphorylates CtIP at S723 to disrupt the CtIP-DNA2 interaction, thereby inhibiting CtIP stimulation of DNA2 long-range resection; the CtIP-F728E-Y736E separation-of-function mutant loses DNA2 interaction/stimulation while retaining MRN stimulation; CDK-dependent CtIP phosphorylation activates MRN-resection in S phase, while PLK1-mediated phosphorylation attenuates DNA2-dependent long-range resection at G2/M. AlphaFold2 structural modeling; separation-of-function mutagenesis; in vitro kinase assay; co-immunoprecipitation; cellular RPA/resection assays; drug sensitivity assays Genes & development High 36746606
2025 At ssDNA gaps (as opposed to DSBs), DNA2-WRN/BLM specifically resects the 5' end of the gap independently of MRN-CtIP; MRN instead resects gaps in the 3'→5' direction using its pCtIP-stimulated exonuclease activity; excessive DNA2-mediated gap resection in BRCA1-deficient cells treated with PARP inhibitors enlarges gaps, impairing their repair. Single-molecule DNA fiber analysis; electron microscopy; in vitro biochemical reconstitution with purified proteins; ssDNA gap substrates Genes & development Medium 40127955

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends. Cell 874 18805091
2011 BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes & development 590 21325134
2010 DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2. Nature 383 20811461
2015 DNA2 drives processing and restart of reversed replication forks in human cells. The Journal of cell biology 295 25733713
2002 Okazaki fragment maturation in yeast. I. Distribution of functions between FEN1 AND DNA2. The Journal of biological chemistry 202 12424238
1997 A yeast replicative helicase, Dna2 helicase, interacts with yeast FEN-1 nuclease in carrying out its essential function. Molecular and cellular biology 194 9121462
2008 Human DNA2 is a mitochondrial nuclease/helicase for efficient processing of DNA replication and repair intermediates. Molecular cell 188 18995831
2010 Saccharomyces cerevisiae Mre11/Rad50/Xrs2 and Ku proteins regulate association of Exo1 and Dna2 with DNA breaks. The EMBO journal 181 20834227
2014 DNA2 cooperates with the WRN and BLM RecQ helicases to mediate long-range DNA end resection in human cells. The Journal of biological chemistry 180 25122754
2006 Evidence suggesting that Pif1 helicase functions in DNA replication with the Dna2 helicase/nuclease and DNA polymerase delta. Molecular and cellular biology 179 16537895
2009 Human Dna2 is a nuclear and mitochondrial DNA maintenance protein. Molecular and cellular biology 159 19487465
2000 Characterization of the enzymatic properties of the yeast dna2 Helicase/endonuclease suggests a new model for Okazaki fragment processing. The Journal of biological chemistry 159 10984490
1995 DNA2 encodes a DNA helicase essential for replication of eukaryotic chromosomes. The Journal of biological chemistry 151 7592912
2011 Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation. Nature structural & molecular biology 148 21841787
2012 The intra-S phase checkpoint targets Dna2 to prevent stalled replication forks from reversing. Cell 140 22682245
2013 Mammalian DNA2 helicase/nuclease cleaves G-quadruplex DNA and is required for telomere integrity. The EMBO journal 135 23604072
2000 The nuclease activity of the yeast DNA2 protein, which is related to the RecB-like nucleases, is essential in vivo. The Journal of biological chemistry 125 10748138
1999 Dna2 mutants reveal interactions with Dna polymerase alpha and Ctf4, a Pol alpha accessory factor, and show that full Dna2 helicase activity is not essential for growth. Genetics 121 10101169
2015 Dna2 nuclease-helicase structure, mechanism and regulation by Rpa. eLife 113 26491943
1998 Dna2 of Saccharomyces cerevisiae possesses a single-stranded DNA-specific endonuclease activity that is able to act on double-stranded DNA in the presence of ATP. The Journal of biological chemistry 112 9756935
2020 Ubiquitinated-PCNA protects replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly. Nature communications 109 32358495
2013 Mutations in DNA2 link progressive myopathy to mitochondrial DNA instability. American journal of human genetics 109 23352259
2013 Lagging strand maturation factor Dna2 is a component of the replication checkpoint initiation machinery. Genes & development 95 23355394
2003 Dna2 helicase/nuclease causes replicative fork stalling and double-strand breaks in the ribosomal DNA of Saccharomyces cerevisiae. The Journal of biological chemistry 94 12686542
2020 Multiple roles of DNA2 nuclease/helicase in DNA metabolism, genome stability and human diseases. Nucleic acids research 90 31754720
2009 Pif1 helicase lengthens some Okazaki fragment flaps necessitating Dna2 nuclease/helicase action in the two-nuclease processing pathway. The Journal of biological chemistry 90 19605347
2006 Biochemical analysis of human Dna2. Nucleic acids research 88 16595800
2016 A Selective Small Molecule DNA2 Inhibitor for Sensitization of Human Cancer Cells to Chemotherapy. EBioMedicine 82 27211550
2012 DNA2 and EXO1 in replication-coupled, homology-directed repair and in the interplay between HDR and the FA/BRCA network. Cell cycle (Georgetown, Tex.) 81 22987153
2000 Genetic analyses of Schizosaccharomyces pombe dna2(+) reveal that dna2 plays an essential role in Okazaki fragment metabolism. Genetics 81 10880469
2003 Formation of a PNA2-DNA2 hybrid quadruplex. Journal of the American Chemical Society 78 12670232
2008 Processing of G4 DNA by Dna2 helicase/nuclease and replication protein A (RPA) provides insights into the mechanism of Dna2/RPA substrate recognition. The Journal of biological chemistry 77 18593712
2000 The endonuclease activity of the yeast Dna2 enzyme is essential in vivo. Nucleic acids research 74 10908349
2012 Human nuclease/helicase DNA2 alleviates replication stress by promoting DNA end resection. Cancer research 71 22491672
2010 Dna2 on the road to Okazaki fragment processing and genome stability in eukaryotes. Critical reviews in biochemistry and molecular biology 69 20131965
2000 The pattern of sensitivity of yeast dna2 mutants to DNA damaging agents suggests a role in DSB and postreplication repair pathways. Mutation research 66 10812329
2020 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 65 32241893
2016 Human DNA2 possesses a cryptic DNA unwinding activity that functionally integrates with BLM or WRN helicases. eLife 65 27612385
2014 Multifaceted role of the Topo IIIα-RMI1-RMI2 complex and DNA2 in the BLM-dependent pathway of DNA break end resection. Nucleic acids research 65 25200081
2002 Coupling of DNA helicase and endonuclease activities of yeast Dna2 facilitates Okazaki fragment processing. The Journal of biological chemistry 65 12004053
2008 Identification of the Xenopus DNA2 protein as a major nuclease for the 5'->3' strand-specific processing of DNA ends. Nucleic acids research 63 18820296
2017 Enhancement of BLM-DNA2-Mediated Long-Range DNA End Resection by CtIP. Cell reports 62 29020620
2003 The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants. Proceedings of the National Academy of Sciences of the United States of America 60 12826610
2014 Preventing over-resection by DNA2 helicase/nuclease suppresses repair defects in Fanconi anemia cells. Cell cycle (Georgetown, Tex.) 58 24626199
2009 Interplay of Mre11 nuclease with Dna2 plus Sgs1 in Rad51-dependent recombinational repair. PloS one 58 19165339
2009 Acetylation of Dna2 endonuclease/helicase and flap endonuclease 1 by p300 promotes DNA stability by creating long flap intermediates. The Journal of biological chemistry 58 20019387
2004 Fission yeast Dna2 is required for generation of the telomeric single-strand overhang. Molecular and cellular biology 58 15485922
2003 Evidence that yeast SGS1, DNA2, SRS2, and FOB1 interact to maintain rDNA stability. Mutation research 58 14643435
2017 Inhibition of DNA2 nuclease as a therapeutic strategy targeting replication stress in cancer cells. Oncogenesis 55 28414320
2012 Okazaki fragment processing-independent role for human Dna2 enzyme during DNA replication. The Journal of biological chemistry 54 22570476
1997 Characterization of Saccharomyces cerevisiae dna2 mutants suggests a role for the helicase late in S phase. Molecular biology of the cell 53 9398673
2006 Isolation of human Dna2 endonuclease and characterization of its enzymatic properties. Nucleic acids research 52 16595799
2003 Bimodal interaction between replication-protein A and Dna2 is critical for Dna2 function both in vivo and in vitro. Nucleic acids research 51 12799426
2013 Nuclease activity of Saccharomyces cerevisiae Dna2 inhibits its potent DNA helicase activity. Proceedings of the National Academy of Sciences of the United States of America 49 23671118
2012 Cross talk between the nuclease and helicase activities of Dna2: role of an essential iron-sulfur cluster domain. Nucleic acids research 45 22684504
2015 Caffeine impairs resection during DNA break repair by reducing the levels of nucleases Sae2 and Dna2. Nucleic acids research 43 26019182
2015 Relative contribution of four nucleases, CtIP, Dna2, Exo1 and Mre11, to the initial step of DNA double-strand break repair by homologous recombination in both the chicken DT40 and human TK6 cell lines. Genes to cells : devoted to molecular & cellular mechanisms 43 26525166
2016 A DNA2 Homolog Is Required for DNA Damage Repair, Cell Cycle Regulation, and Meristem Maintenance in Plants. Plant physiology 42 26951435
2017 The motor activity of DNA2 functions as an ssDNA translocase to promote DNA end resection. Genes & development 41 28336515
2001 Tripartite structure of Saccharomyces cerevisiae Dna2 helicase/endonuclease. Nucleic acids research 41 11452032
2014 The 9-1-1 checkpoint clamp stimulates DNA resection by Dna2-Sgs1 and Exo1. Nucleic acids research 40 25122752
2008 DNA2 resolves expanding flap in mitochondrial base excision repair. Molecular cell 40 19026774
2000 Identification of the Xenopus laevis homolog of Saccharomyces cerevisiae DNA2 and its role in DNA replication. The Journal of biological chemistry 40 10636853
2010 Xenopus DNA2 is a helicase/nuclease that is found in complexes with replication proteins And-1/Ctf4 and Mcm10 and DSB response proteins Nbs1 and ATM. Cell cycle (Georgetown, Tex.) 39 20237432
2008 Dynamic removal of replication protein A by Dna2 facilitates primer cleavage during Okazaki fragment processing in Saccharomyces cerevisiae. The Journal of biological chemistry 39 18799459
2017 A novel role of the Dna2 translocase function in DNA break resection. Genes & development 37 28336516
2015 The Saccharomyces cerevisiae Dna2 can function as a sole nuclease in the processing of Okazaki fragments in DNA replication. Nucleic acids research 37 26175049
2009 Dna2 is a structure-specific nuclease, with affinity for 5'-flap intermediates. Nucleic acids research 37 19934252
2019 Regulatory control of Sgs1 and Dna2 during eukaryotic DNA end resection. Proceedings of the National Academy of Sciences of the United States of America 36 30850524
2011 Inviability of a DNA2 deletion mutant is due to the DNA damage checkpoint. Cell cycle (Georgetown, Tex.) 36 21508669
2018 Dna2 nuclease deficiency results in large and complex DNA insertions at chromosomal breaks. Nature 34 30518856
2018 Dna2 processes behind the fork long ssDNA flaps generated by Pif1 and replication-dependent strand displacement. Nature communications 31 30446656
2012 Biochemical analyses indicate that binding and cleavage specificities define the ordered processing of human Okazaki fragments by Dna2 and FEN1. Nucleic acids research 31 22570407
2016 Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1. Nature communications 29 27779184
2015 BRCA1 and CtIP Are Both Required to Recruit Dna2 at Double-Strand Breaks in Homologous Recombination. PloS one 29 25909997
2005 Enzymatic properties of the Caenorhabditis elegans Dna2 endonuclease/helicase and a species-specific interaction between RPA and Dna2. Nucleic acids research 29 15745997
2005 Genetic and physical interactions between Schizosaccharomyces pombe Mcl1 and Rad2, Dna2 and DNA polymerase alpha: evidence for a multifunctional role of Mcl1 in DNA replication and repair. Current genetics 29 15915339
2017 DNA2-An Important Player in DNA Damage Response or Just Another DNA Maintenance Protein? International journal of molecular sciences 28 28718810
2015 Yet another job for Dna2: Checkpoint activation. DNA repair 27 25956863
2010 Dna2 exhibits a unique strand end-dependent helicase function. The Journal of biological chemistry 27 20929864
2009 Significance of the dissociation of Dna2 by flap endonuclease 1 to Okazaki fragment processing in Saccharomyces cerevisiae. The Journal of biological chemistry 27 19179330
2014 The DNA2 nuclease/helicase is an estrogen-dependent gene mutated in breast and ovarian cancers. Oncotarget 26 25238049
2006 Single strand annealing and ATP-independent strand exchange activities of yeast and human DNA2: possible role in Okazaki fragment maturation. The Journal of biological chemistry 26 17032657
1999 Banana bunchy top virus DNA-2 to 6 are monocistronic. Archives of virology 26 10076511
1998 Semi-conservative replication in yeast nuclear extracts requires Dna2 helicase and supercoiled template. Journal of molecular biology 26 9710536
2019 Biallelic variants in DNA2 cause microcephalic primordial dwarfism. Human mutation 25 31045292
2006 Flap endonuclease disengages Dna2 helicase/nuclease from Okazaki fragment flaps. The Journal of biological chemistry 25 17038322
1993 Formation of a cleavasome: enhancer DNA-2 stabilizes an active conformation of NaeI dimer. Biochemistry 25 8347627
2019 TRAF6 mediates human DNA2 polyubiquitination and nuclear localization to maintain nuclear genome integrity. Nucleic acids research 24 31216032
2018 A DNA nick at Ku-blocked double-strand break ends serves as an entry site for exonuclease 1 (Exo1) or Sgs1-Dna2 in long-range DNA end resection. The Journal of biological chemistry 23 30224356
2016 Nucleolytic processing of aberrant replication intermediates by an Exo1-Dna2-Sae2 axis counteracts fork collapse-driven chromosome instability. Nucleic acids research 22 27672038
2004 Genetics of lagging strand DNA synthesis and maturation in fission yeast: suppression analysis links the Dna2-Cdc24 complex to DNA polymerase delta. Nucleic acids research 22 15576681
2023 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 21 37526271
2021 Distinct RPA domains promote recruitment and the helicase-nuclease activities of Dna2. Nature communications 21 34764291
2019 Nej1 Interacts with Mre11 to Regulate Tethering and Dna2 Binding at DNA Double-Strand Breaks. Cell reports 21 31390569
2017 Dna2 initiates resection at clean DNA double-strand breaks. Nucleic acids research 21 28981724
2014 Fission yeast Pxd1 promotes proper DNA repair by activating Rad16XPF and inhibiting Dna2. PLoS biology 20 25203555
2025 MRN-CtIP, EXO1, and DNA2-WRN/BLM act bidirectionally to process DNA gaps in PARPi-treated cells without strand cleavage. Genes & development 19 40127955
2024 EXO1 and DNA2-mediated ssDNA gap expansion is essential for ATR activation and to maintain viability in BRCA1-deficient cells. Nucleic acids research 19 38721777
2023 PLK1 regulates CtIP and DNA2 interplay in long-range DNA end resection. Genes & development 18 36746606

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