Affinage

TWNK

Twinkle mtDNA helicase · UniProt Q96RR1

Length
684 aa
Mass
77.2 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 24 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

TWNK (TWINKLE) is the essential replicative DNA helicase of mammalian mitochondria, a nucleoid-associated protein structurally related to the phage T7 gene 4 primase/helicase that is required for maintenance of the mitochondrial genome (PMID:11431692, PMID:23393161). It is a 5'→3' helicase that unwinds duplex DNA from a single-stranded 5'-overhang bearing a short 3'-tail, has an absolute requirement for NTP hydrolysis with UTP as the optimal cofactor, and is specifically stimulated by mitochondrial single-stranded DNA-binding protein (mtSSB), which boosts unwinding rate and dramatically extends translocation processivity (PMID:12975372, PMID:32213598). TWINKLE assembles into hexameric — and heptameric — rings whose subunits switch between open and closed configurations, with NTP binding driving large-scale conformational changes; the N-terminal domain mediates single-stranded DNA binding and replisome processivity, and an N-terminal ZBD/RPD layer and a RecA-like CTD layer contact in trans within the ring (PMID:25824949, PMID:30496414, PMID:32213598, PMID:18039713). Unlike T7 gp4, TWINKLE loads onto closed circular mtDNA without a dedicated loader and can initiate replication together with mtSSB and POLG (PMID:18039713, PMID:21840902). It is the sole helicase for both full-length mtDNA replication and D-loop strand synthesis, with reversible loading at the coreTAS element gating the switch between abortive D-loop formation and complete replication (PMID:23393161, PMID:26253742). Beyond unwinding, TWINKLE catalyzes DNA strand annealing, NTP-dependent homologous strand exchange, and branch migration of three- and four-way junctions, implicating it in recombinational repair, while it unwinds G-quadruplex substrates only inefficiently and is inhibited by oxidative lesions and DNA-bound TFAM (PMID:22383523, PMID:26887820, PMID:27226550, PMID:25193669). Autosomal-dominant progressive external ophthalmoplegia (adPEO) is caused by mutations in the TWINKLE linker and N-terminal domains that abolish hexamerization, disrupt NTP-dependent conformational changes, ssDNA binding, and ATPase–helicase coupling, producing replication stalling and the accumulation of multiple mtDNA deletions or mtDNA depletion (PMID:11431692, PMID:16301523, PMID:18279890, PMID:19084593, PMID:30496414).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2001 High

    Establishing that an unknown adPEO disease gene encodes a mitochondrial nucleoid protein resembling a phage replicative helicase placed TWINKLE at the heart of mtDNA maintenance.

    Evidence Colocalization imaging with mtDNA, sequence analysis, and adPEO pedigree genetics

    PMID:11431692

    Open questions at the time
    • Did not demonstrate helicase activity biochemically
    • Molecular mechanism linking mutations to disease unresolved
  2. 2003 High

    Defining TWINKLE's biochemical activity answered what enzyme it is: a 5'→3' DNA helicase with defined substrate, NTP, and cofactor requirements.

    Evidence Helicase, NTP-specificity, and mtSSB-stimulation assays with purified recombinant protein

    PMID:12975372

    Open questions at the time
    • Oligomeric state during unwinding not yet defined
    • Mechanism of mtSSB stimulation unresolved
  3. 2004 High

    Gain- and loss-of-function in mice and human cells established that TWINKLE dosage directly controls mtDNA copy number in vivo.

    Evidence Transgenic mouse overexpression and RNAi knockdown with copy-number quantification

    PMID:15509589

    Open questions at the time
    • Did not address how copy number is regulated mechanistically
  4. 2005 High

    A PEO-mutant mouse demonstrated that TWINKLE dysfunction is sufficient to drive the multiple mtDNA deletions and respiratory pathology seen in patients.

    Evidence Transgenic mouse expressing PEO-mutant Twinkle with histological, genetic, and respiratory chain analysis

    PMID:16301523

    Open questions at the time
    • Did not resolve the molecular step at which mutant helicase fails
  5. 2007 Medium

    Cell-based and biochemical analyses showed that catalytically deficient TWINKLE stalls mtDNA replication, producing fully double-stranded intermediates distinct from POLG-mutant stalling, and that the N-terminal domain mediates ssDNA binding and processivity.

    Evidence Dominant-negative mutant expression with 2D gel electrophoresis, ddC inhibitor rescue, recombinant T457I assays, and N-terminal truncation analysis

    PMID:17452351 PMID:17722119 PMID:18039713

    Open questions at the time
    • Single-lab activity measurements for some mutants
    • How TWINKLE loads onto closed circular DNA without a loader unresolved at this stage
  6. 2008 High

    Systematic biochemical dissection of linker and N-terminal adPEO mutations linked specific defects in hexamerization, ATPase activity, ssDNA-binding coupling, and replication competence to distinct disease alleles.

    Evidence ATPase/helicase/hexamerization assays on multiple mutants, in vitro replication, 2D gels, Deletor mouse muscle, and T7 gp4-based structural modeling

    PMID:18279890 PMID:18971204 PMID:19084593

    Open questions at the time
    • Structural basis inferred from homology modeling, not direct TWINKLE structure
    • Genotype–phenotype severity correlations incomplete
  7. 2011 High

    Reconstitution on a closed circular template established that TWINKLE loads without a dedicated loader and initiates synthesis with mtSSB and POLG, mirroring in vivo replication initiation.

    Evidence In vitro reconstitution with purified TWINKLE, mtSSB, POLG and primer extension

    PMID:21840902

    Open questions at the time
    • Loading mechanism onto closed circular DNA not structurally defined
  8. 2012 High

    Biochemical work revealed that TWINKLE possesses strand-annealing activity opposing unwinding and multiple ssDNA-binding sites, expanding its repertoire beyond a simple helicase.

    Evidence Annealing/helicase assays, fluorescence anisotropy competition binding, and analytical ultracentrifugation

    PMID:22383523

    Open questions at the time
    • Physiological context of annealing activity unresolved
    • Regulation of unwinding-vs-annealing balance unclear
  9. 2012 Medium

    Model-organism and neuronal studies extended TWINKLE's relevance to age-related neurodegeneration and uncovered a Parkin connection and conserved dominant-negative mutant behavior.

    Evidence Drosophila UAS-GAL4 genetics with OXPHOS/apoptosis readouts; DA-neuron mouse model with Parkin co-IP, colocalization, and proteasome rescue

    PMID:22949510 PMID:22952820

    Open questions at the time
    • TWINKLE–Parkin interaction shown by single-lab co-IP without reciprocal structural validation
    • Mechanism linking mtDNA deletions to Parkin/proteasome changes unresolved
  10. 2013 High

    A conditional knockout proved TWINKLE is the sole and essential replicative helicase for both full-length mtDNA and D-loop H-strand synthesis, and is required for embryonic development.

    Evidence Cre-lox conditional knockout mouse with Southern blot, 2D gels, and D-loop strand synthesis assays

    PMID:23393161

    Open questions at the time
    • Did not address any non-replicative roles in vivo
  11. 2013 Medium

    Colocalization and depletion experiments revealed a role for TWINKLE in organizing mitochondrial RNA granules independent of RNA synthesis or processing.

    Evidence Immunofluorescence colocalization, siRNA depletion, and pulldown of RNA granule proteins including GRSF1

    PMID:30715486

    Open questions at the time
    • Mechanism by which TWINKLE structures RNA granules unknown
    • Direct vs indirect interaction with GRSF1 not resolved
  12. 2015 Medium

    Reversible TWINKLE loading at coreTAS was shown to gate the choice between abortive D-loop formation and complete replication, integrating helicase loading with transcription termination signals.

    Evidence Comparative genomics, in vitro transcription termination, and TWINKLE loading/displacement assays

    PMID:26253742

    Open questions at the time
    • Regulator controlling the switch in vivo unidentified
    • Single-lab in vitro system
  13. 2016 High

    Demonstration of NTP-dependent homologous strand exchange and branch migration of three- and four-way junctions implicated TWINKLE in recombinational repair of mtDNA, and mapped inhibition by oxidative lesions and TFAM.

    Evidence In vitro strand-exchange, branch-migration, oxidative-lesion, single-molecule FRET, and TFAM inhibition assays

    PMID:26887820 PMID:27226550

    Open questions at the time
    • In vivo evidence for recombinational repair role lacking
    • Physiological partners for strand exchange not defined
  14. 2015 High

    Structural determination of the TWINKLE hexamer defined its two-layered ring architecture and revealed coexisting hexa- and heptameric conformations in solution.

    Evidence Single-particle electron microscopy, SAXS, and atomic model building

    PMID:25824949

    Open questions at the time
    • Did not capture DNA-bound or NTP-driven states
    • Functional role of heptamer vs hexamer unclear
  15. 2020 High

    Single-molecule imaging directly visualized ring open/close transitions, quantified unwinding rate, and showed mtSSB increases processivity several-fold, linking conformational dynamics to function.

    Evidence AFM imaging and single-molecule unwinding/translocation processivity measurements ± mtSSB

    PMID:32213598

    Open questions at the time
    • Coordination with POLG at the replisome not addressed
    • Mechanism of mtSSB-mediated processivity gain unresolved
  16. 2022 High

    Cryo-EM of full-length human TWINKLE variants defined the multimeric interfaces, mapped clinical disease mutations onto the structure, and showed that adPEO mutations abolish NTP-dependent conformational changes and alter ring closure or subunit number.

    Evidence Cryo-EM, crosslinking-MS, and molecular dynamics simulations of W315L and other adPEO variants

    PMID:30496414 PMID:35914129

    Open questions at the time
    • No structure of a fully active wild-type DNA-engaged unwinding complex
    • Replisome-level structures with POLG and mtSSB lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TWINKLE's strand-annealing, strand-exchange, and branch-migration activities are deployed in vivo for recombinational repair, and how its RNA-granule organizing role and Parkin interaction integrate with its replicative function, remain open.
  • No in vivo demonstration of mtDNA recombinational repair role
  • Mechanism of RNA granule organization unknown
  • Functional significance of TWINKLE–Parkin interaction unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 5 GO:0003677 DNA binding 3 GO:0140657 ATP-dependent activity 3 GO:0016787 hydrolase activity 2
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-1643685 Disease 3 R-HSA-69306 DNA Replication 3 R-HSA-73894 DNA Repair 2
Partners
GRSF1POLGPRKNSSBP1TFAM
Complex memberships
mitochondrial nucleoidmtDNA replisome

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 TWINKLE is a mitochondrial protein with structural similarity to phage T7 gene 4 primase/helicase that colocalizes with mtDNA in mitochondrial nucleoids, establishing its role in mtDNA maintenance. Subcellular localization by colocalization imaging; sequence analysis; genetic screening of adPEO pedigrees identifying 11 coding-region mutations co-segregating with disease Nature genetics High 11431692
2003 TWINKLE is a 5'→3' DNA helicase that requires a 10-nucleotide single-stranded 5'-overhang plus a short 3'-tail for duplex unwinding, has an absolute requirement for NTP hydrolysis (optimal substrate UTP), and is specifically stimulated by mitochondrial single-stranded DNA-binding protein (mtSSB). Biochemical characterization of purified recombinant TWINKLE: helicase assays with defined substrates, NTP specificity assays, stimulation assays with mtSSB The Journal of biological chemistry High 12975372
2004 TWINKLE is essential for mtDNA maintenance in vivo; overexpression of wild-type Twinkle in transgenic mice increases mtDNA copy number up to 3-fold, and RNAi-mediated knockdown in human cells causes rapid mtDNA copy number depletion. Transgenic mouse overexpression; RNAi knockdown in cultured human cells; mtDNA copy number quantification Human molecular genetics High 15509589
2005 Expression of mutant Twinkle (PEO patient mutations) in transgenic mice causes accumulation of multiple mtDNA deletions, progressive respiratory chain dysfunction, and late-onset mitochondrial myopathy, demonstrating that Twinkle dysfunction directly drives mtDNA deletion formation. Transgenic mouse model expressing PEO-mutant Twinkle; histological, genetic, and biochemical analysis of muscle; Southern blot for mtDNA deletions; respiratory chain enzyme assays Proceedings of the National Academy of Sciences of the United States of America High 16301523
2007 The T457I recessive Twinkle mutation causes defective helicase activity as demonstrated with purified recombinant mutant protein, and T457 is located at the monomer-monomer interface of the hexameric enzyme based on structural modeling. Purified recombinant T457I mutant protein helicase activity assay in vitro; structural modeling of hexameric interface Annals of neurology Medium 17722119
2007 Expression of catalytically deficient Twinkle mutants in human cells causes severe mtDNA replication stalling resulting in fully double-stranded replication intermediates, distinct from POLG1-mutant stalling which still shows delayed lagging-strand synthesis; limited POLG inhibition restores lagging-strand delay in Twinkle-stalled cells. Expression of dominant-negative Twinkle mutants in human cell culture; two-dimensional agarose gel electrophoresis of replication intermediates; pharmacological inhibition with dideoxycytidine Nucleic acids research Medium 17452351
2007 The N-terminal domain of TWINKLE is required for efficient single-stranded DNA binding; truncation of this region reduces DNA helicase activity and mtDNA replisome processivity. TWINKLE differs from phage T7 gp4 in that it binds double-stranded DNA and forms stable hexamers even without Mg2+ or NTPs, suggesting it requires an accessory helicase loader for loading onto circular mtDNA. N-terminal truncation mutants; ssDNA binding assays; helicase activity assays; in vitro replisome processivity assays; comparison with T7 gp4 Nucleic acids research High 18039713
2008 Seven adPEO-causing mutations in the TWINKLE linker region produce distinct molecular phenotypes: some completely abolish hexamerization and helicase activity, others show subtler effects; a structural model based on T7 gp4 explains these phenotypes and predicts consequences of other adPEO mutations. Biochemical characterization of seven linker-region mutants (ATPase, helicase, hexamerization assays); molecular modeling based on T7 gp4 crystal structure Journal of molecular biology High 18279890
2008 Four adPEO-causing mutations (W315L, K319T, R334Q, P335L) in the N-terminal domain of TWINKLE cause dramatically decreased ATPase activity (partially rescued by ssDNA), defective helicase activity, and cannot support normal mtDNA replication; structural modeling localizes these mutations to the ssDNA-binding region, implicating disrupted ssDNA binding/ATP hydrolysis coupling. Biochemical characterization of N-terminal adPEO mutants: ATPase assays ± ssDNA, helicase assays, in vitro replication assays; molecular modeling Biochimica et biophysica acta High 19084593
2008 Expression of dominant adPEO Twinkle mutations in human cells causes accumulation of mtDNA replication intermediates (replication pausing/stalling) and mtDNA depletion; the Deletor mouse model shows strongly enhanced replication intermediates even before late-onset mtDNA deletions accumulate; in vitro assays confirm functional defects in multiple adPEO Twinkle mutants. Human cell culture expression of adPEO mutants; two-dimensional gel electrophoresis of replication intermediates; analysis of Deletor mouse muscle; in vitro helicase assays Human molecular genetics High 18971204
2011 TWINKLE can load onto a closed circular DNA template without a specialized helicase loader and can support initiation of DNA synthesis by the mitochondrial replication machinery, closely resembling initiation of mtDNA synthesis in vivo. In vitro reconstitution of mtDNA replication on closed circular template with purified TWINKLE, mtSSB, and POLG; primer extension assays Nucleic acids research High 21840902
2012 TWINKLE has DNA strand-annealing activity that opposes unwinding in the absence of accessory proteins; it assembles into hexamers and higher oligomers (MgUTP stabilizes hexamers); it possesses more than one ssDNA-binding site; ssDNA but not dsDNA inhibits annealing, suggesting dsDNA binds a distinct site. Purified recombinant TWINKLE from E. coli; helicase and annealing assays; fluorescence anisotropy competition binding; analytical ultracentrifugation for oligomeric state The Journal of biological chemistry High 22383523
2013 TWINKLE is the sole replicative DNA helicase in mammalian mitochondria and is essential for mouse embryonic development; conditional knockout of Twinkle causes rapid, severe mtDNA depletion in heart and skeletal muscle with complete loss of replication intermediates; TWINKLE is also essential for nascent H-strand synthesis in the D-loop, indicating no separate helicase for D-loop replication. Conditional knockout mouse (Cre-lox); Southern blot for mtDNA; two-dimensional gel electrophoresis for replication intermediates; D-loop strand synthesis assays Human molecular genetics High 23393161
2013 TWINKLE colocalizes with mitochondrial RNA granules and nucleoids; short-term TWINKLE depletion greatly diminishes RNA granules without inhibiting RNA synthesis or processing; TWINKLE can serve as bait to enrich RNA granule proteins including GRSF1, demonstrating a role for TWINKLE in mitochondrial RNA organization. Immunofluorescence colocalization; siRNA depletion; co-immunoprecipitation/pulldown with RNA granule proteins; RNA processing analysis Nucleic acids research Medium 30715486
2014 Purified recombinant TWINKLE helicase inefficiently unwinds G-quadruplex (G4) DNA substrates (intermolecular, intramolecular, and disease-relevant unimolecular G4); mitochondrial G4-forming sequences cluster near deletion breakpoints in human disease, suggesting G4 structures are roadblocks to Twinkle-mediated replication. In vitro helicase unwinding assays on defined G4 substrates with purified TWINKLE; circular dichroism and UV spectral analysis of G4 structure formation; computational G4 predictor analysis The Journal of biological chemistry High 25193669
2015 TWINKLE loading at the coreTAS sequence element at the 3'-end of the D-loop is reversible, and this site controls the switch between abortive D-loop formation and complete mtDNA replication; both light- and heavy-strand transcription terminate at conserved D-loop sequence motifs (CSB1 and coreTAS respectively). Comparative genomics identification of conserved motifs; in vitro transcription termination assays; TWINKLE loading and displacement assays at coreTAS Nucleic acids research Medium 26253742
2015 TWINKLE hexameric structure determined by electron microscopy and SAXS reveals a two-layered ring comprising ZBD/RPD domains in one layer and CTD (RecA-like) in another; contacts in trans between adjacent subunits occur between ZBDs and RPDs, and between RPDs and CTDs; ZBDs show structural heterogeneity; in solution a mixture of hexa- and heptameric conformations exists. Electron microscopy (single-particle); small-angle X-ray scattering (SAXS); atomic model building Nucleic acids research High 25824949
2016 TWINKLE catalyzes homologous strand-exchange between unwinding substrates and complementary ssDNA via coupled unwinding and annealing; strand-exchange requires NTP hydrolysis and is promoted by short regions of homology; TWINKLE also catalyzes branch migration of four-way junction DNA, suggesting a role in recombinational repair of mtDNA. In vitro strand-exchange assays with purified TWINKLE on defined substrates; branch migration assays on synthetic Holliday junctions; NTP hydrolysis requirement tested with non-hydrolyzable analogs Nucleic acids research High 26887820
2016 TWINKLE efficiently dissociates D-loop substrates regardless of whether the invading strand has a 5' or 3' tail; TWINKLE branch-migrates three-stranded DNA with strong 5'→3' directionality; TWINKLE unwinding is inhibited by oxidative DNA lesions in a lesion-type and strand-dependent manner; TFAM binding to DNA inhibits TWINKLE unwinding. In vitro helicase assays on D-loop, fork, and branch migration substrates; site-specific oxidative lesion substrates; single-molecule FRET; TFAM inhibition assays The Journal of biological chemistry High 27226550
2019 Cryo-EM structures of TWINKLE W315L reveal oligomeric assemblies and define the multimeric interface; wild-type TWINKLE undergoes large-scale conformational changes upon NTP binding that are lost in adPEO disease variants; disease mutations alter oligomeric properties including those that destroy linker flexibility, inhibit ring closure, or change subunit number within the helicase ring. Cryo-electron microscopy (cryo-EM); crosslinking-mass spectrometry; molecular dynamics simulations; single-particle analysis of multiple adPEO variants Human molecular genetics High 30496414
2020 Single-molecule AFM imaging reveals TWINKLE subunits self-assemble into hexamers and higher-order complexes that switch between open and closed-ring configurations; closed-ring conformers unwind ~240 bp/min; mtSSB stimulates unwinding ~5-fold and increases translocation processivity from ~1750 to >9000 bp per binding event. Atomic force microscopy (AFM) imaging in air and liquid; single-molecule helicase unwinding assays; translocation processivity measurements with and without mtSSB The Journal of biological chemistry High 32213598
2022 Cryo-EM structures of full-length human TWINKLE W315L characterize its oligomeric assemblies, define multimeric interfaces, and map clinical disease variants; crosslinking-MS and MD simulations reveal dynamic movement and molecular consequences of the W315L variant on helicase ring dynamics. Cryo-electron microscopy; crosslinking-mass spectrometry; molecular dynamics simulations Proceedings of the National Academy of Sciences of the United States of America High 35914129
2012 Mutant Twinkle expression in dopaminergic neurons of mice increases age-related mtDNA deletions and reduces DA neuron number; Twinkle co-immunoprecipitates and colocalizes with Parkin in mitochondria; mutant Twinkle reduces Parkin expression and Parkin overexpression rescues proteasome activity reduction caused by mutant Twinkle. Transgenic mouse model targeting DA neurons; co-immunoprecipitation; confocal colocalization; proteasome activity assays; Parkin overexpression rescue in PC12 cells Human molecular genetics Medium 22949510
2012 Overexpression of wild-type d-mtDNA helicase (Drosophila TWINKLE ortholog) increases mtDNA copy number; helicase active-site mutation K388A causes severe mtDNA depletion and lethality; adPEO-equivalent mutation A442P has a dominant-negative effect similar to K388A; W441C mutation causes moderate mtDNA reduction; mitochondrial OXPHOS defects caused by these mutations promote apoptosis in Drosophila. UAS-GAL4 overexpression system in Drosophila; mtDNA copy number quantification; phenotypic analysis; OXPHOS activity assays; apoptosis markers PloS one Medium 22952820

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. Nature genetics 679 11431692
2005 Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice. Proceedings of the National Academy of Sciences of the United States of America 280 16301523
1989 Protein-resistant surfaces prepared by PEO-containing block copolymer surfactants. Journal of biomedical materials research 250 2715159
2003 TWINKLE Has 5' -> 3' DNA helicase activity and is specifically stimulated by mitochondrial single-stranded DNA-binding protein. The Journal of biological chemistry 231 12975372
2004 Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number. Human molecular genetics 205 15509589
2002 PEO-like plasma polymerized tetraglyme surface interactions with leukocytes and proteins: in vitro and in vivo studies. Journal of biomaterials science. Polymer edition 168 12160299
2005 Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky. Human molecular genetics 155 16135556
2013 TWINKLE is an essential mitochondrial helicase required for synthesis of nascent D-loop strands and complete mtDNA replication. Human molecular genetics 144 23393161
2007 Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion. Annals of neurology 134 17722119
2002 Engineering protein and cell adhesivity using PEO-terminated triblock polymers. Journal of biomedical materials research 131 11835168
2019 Thermosensitive Hydrogel Based on PEO-PPO-PEO Poloxamers for a Controlled In Situ Release of Recombinant Adeno-Associated Viral Vectors for Effective Gene Therapy of Cartilage Defects. Advanced materials (Deerfield Beach, Fla.) 127 31763733
2015 Overexpression of TFAM or twinkle increases mtDNA copy number and facilitates cardioprotection associated with limited mitochondrial oxidative stress. PloS one 125 25822152
2007 Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG causes distinct replication stalling phenotypes. Nucleic acids research 125 17452351
2003 Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO). Neurology 123 12707443
2008 Twinkle mutations associated with autosomal dominant progressive external ophthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling. Human molecular genetics 118 18971204
2014 DNA sequences proximal to human mitochondrial DNA deletion breakpoints prevalent in human disease form G-quadruplexes, a class of DNA structures inefficiently unwound by the mitochondrial replicative Twinkle helicase. The Journal of biological chemistry 106 25193669
2010 Reducing non-specific binding and uptake of nanoparticles and improving cell targeting with an antifouling PEO-b-PgammaMPS copolymer coating. Biomaterials 96 20398933
2004 Twinkle and POLG defects enhance age-dependent accumulation of mutations in the control region of mtDNA. Nucleic acids research 96 15181170
2001 In vivo gene delivery into ocular tissues by eye drops of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles. Gene therapy 93 11438834
2015 Regulation of DNA replication at the end of the mitochondrial D-loop involves the helicase TWINKLE and a conserved sequence element. Nucleic acids research 86 26253742
2009 Recessive twinkle mutations cause severe epileptic encephalopathy. Brain : a journal of neurology 84 19304794
2014 Mutations in Twinkle primase-helicase cause Perrault syndrome with neurologic features. Neurology 83 25355836
2007 Familial parkinsonism and ophthalmoplegia from a mutation in the mitochondrial DNA helicase twinkle. Archives of neurology 82 17620490
2007 The DNA polymerase gamma Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine. Human molecular genetics 82 17725985
2006 Twinkle, the mitochondrial replicative DNA helicase, is widespread in the eukaryotic radiation and may also be the mitochondrial DNA primase in most eukaryotes. Journal of molecular evolution 82 16612544
2017 Enhanced oral absorption and anticancer efficacy of cabazitaxel by overcoming intestinal mucus and epithelium barriers using surface polyethylene oxide (PEO) decorated positively charged polymer-lipid hybrid nanoparticles. Journal of controlled release : official journal of the Controlled Release Society 80 29133120
1997 Plasma protein adsorption and platelet adhesion onto comb-like PEO gradient surfaces. Journal of biomedical materials research 77 8978659
2005 PEO-PPO-PEO-based poly(ether ester urethane)s as degradable reverse thermo-responsive multiblock copolymers. Biomaterials 76 16310849
2010 The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO. Neurology 67 20479361
2000 In vitro and in vivo studies of PEO-grafted blood-contacting cardiovascular prostheses. Journal of biomaterials science. Polymer edition 64 11263803
1993 Cell-seeding and in vitro biocompatibility evaluation of polymeric matrices of PEO/PBT copolymers and PLLA. Biomaterials 62 8399953
2007 Oil-encapsulating PEO-PPO-PEO/PEG shell cross-linked nanocapsules for target-specific delivery of paclitaxel. Biomacromolecules 60 17291088
2004 Protein resistant polyurethane surfaces by chemical grafting of PEO: amino-terminated PEO as grafting reagent. Colloids and surfaces. B, Biointerfaces 60 15542334
1990 Blood compatibility of PEO grafted polyurethane and HEMA/styrene block copolymer surfaces. Journal of biomedical materials research 60 2211743
2012 Human mitochondrial DNA helicase TWINKLE is both an unwinding and annealing helicase. The Journal of biological chemistry 58 22383523
2020 TWINKLE and Other Human Mitochondrial DNA Helicases: Structure, Function and Disease. Genes 56 32283748
2008 Structure-function defects of the TWINKLE linker region in progressive external ophthalmoplegia. Journal of molecular biology 54 18279890
2019 Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB. Nucleic acids research 52 30715486
2007 The N-terminal domain of TWINKLE contributes to single-stranded DNA binding and DNA helicase activities. Nucleic acids research 52 18039713
2007 Interplay between PEO tether length and ligand spacing governs cell spreading on RGD-modified PMMA-g-PEO comb copolymers. Biomacromolecules 49 17877394
2018 PEO-PPO-PEO Tri-Block Copolymers for Gene Delivery Applications in Human Regenerative Medicine-An Overview. International journal of molecular sciences 46 29518011
2015 The hexameric structure of the human mitochondrial replicative helicase Twinkle. Nucleic acids research 45 25824949
2015 PEO-PPO-PEO micelles as effective rAAV-mediated gene delivery systems to target human mesenchymal stem cells without altering their differentiation potency. Acta biomaterialia 45 26320543
2013 Comprehensive characterization of chitosan/PEO/levan ternary blend films. Carbohydrate polymers 45 24507374
1999 Static and dynamic fibroblast seeding and cultivation in porous PEO/PBT scaffolds. Journal of materials science. Materials in medicine 44 15347949
2019 Polyoxyethylene (PEO)|PEO-Perovskite|PEO Composite Electrolyte for All-Solid-State Lithium Metal Batteries. ACS applied materials & interfaces 43 31765131
2009 Finding twinkle in the eyes of a 71-year-old lady: a case report and review of the genotypic and phenotypic spectrum of TWINKLE-related dominant disease. American journal of medical genetics. Part A 43 19353676
2010 Addition of chitosan to silicate cross-linked PEO for tuning osteoblast cell adhesion and mineralization. ACS applied materials & interfaces 41 20949937
2006 Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay. European journal of human genetics : EJHG 41 16639411
2003 A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia. Neuromuscular disorders : NMD 41 12921794
2013 Overexpression of Twinkle-helicase protects cardiomyocytes from genotoxic stress caused by reactive oxygen species. Proceedings of the National Academy of Sciences of the United States of America 40 24218554
2017 Novel neuro-audiological findings and further evidence for TWNK involvement in Perrault syndrome. Journal of translational medicine 39 28178980
2014 Hemocompatibility and selective cell fate of polydopamine-assisted heparinized PEO/PLLA composite coating on biodegradable AZ31 alloy. Colloids and surfaces. B, Biointerfaces 39 25009102
1997 Grafting of PEO to glass, nitinol, and pyrolytic carbon surfaces by gamma irradiation. Journal of biomedical materials research 39 9421750
2011 The mitochondrial DNA helicase TWINKLE can assemble on a closed circular template and support initiation of DNA synthesis. Nucleic acids research 38 21840902
2014 Electrospun PCL/PEO coaxial fibers for basic fibroblast growth factor delivery. Journal of materials chemistry. B 37 32262212
2002 Clinical and molecular features of adPEO due to mutations in the Twinkle gene. Journal of the neurological sciences 36 12163192
2008 Novel Twinkle (PEO1) gene mutations in mendelian progressive external ophthalmoplegia. Journal of neurology 34 18575922
2008 SIRT1 regulates the ribosomal DNA locus: epigenetic candles twinkle longevity in the Christmas tree. Biochemical and biophysical research communications 34 19010308
2012 Mutant Twinkle increases dopaminergic neurodegeneration, mtDNA deletions and modulates Parkin expression. Human molecular genetics 33 22949510
2008 Structure-function defects of the twinkle amino-terminal region in progressive external ophthalmoplegia. Biochimica et biophysica acta 33 19084593
2016 PEO-PPO-PEO Carriers for rAAV-Mediated Transduction of Human Articular Chondrocytes in Vitro and in a Human Osteochondral Defect Model. ACS applied materials & interfaces 31 27404480
2013 Twinkle mutation in an Italian family with external progressive ophthalmoplegia and parkinsonism: a case report and an update on the state of art. Neuroscience letters 30 24076137
2008 Thiol/acrylate-modified PEO-PPO-PEO triblocks used as reactive and thermosensitive copolymers. Biomacromolecules 30 18710282
2018 Bioactive multi-elemental PEO-coatings on titanium for dental implant applications. Materials science & engineering. C, Materials for biological applications 29 30678963
2010 POLG, but not PEO1, is a frequent cause of cerebellar ataxia in Central Europe. Movement disorders : official journal of the Movement Disorder Society 28 20803511
2016 Homologous DNA strand exchange activity of the human mitochondrial DNA helicase TWINKLE. Nucleic acids research 27 26887820
2016 Twinkle overexpression prevents cardiac rupture after myocardial infarction by alleviating impaired mitochondrial biogenesis. American journal of physiology. Heart and circulatory physiology 27 27342873
2015 Enhancing the protein resistance of silicone via surface-restructuring PEO-silane amphiphiles with variable PEO length. Journal of materials chemistry. B 27 26339488
2016 Interactions of Pluronic nanocarriers with 2D and 3D cell cultures: Effects of PEO block length and aggregation state. Journal of controlled release : official journal of the Controlled Release Society 26 26792572
2016 Mussel-inspired functionalization of PEO/PCL composite coating on a biodegradable AZ31 magnesium alloy. Colloids and surfaces. B, Biointerfaces 25 26874118
2019 Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations: overlap of TWNK-related recessive disorders. Journal of translational medicine 23 31455392
2024 Anti-adhesive and antibacterial chitosan/PEO nanofiber dressings with high breathability for promoting wound healing. International journal of biological macromolecules 22 38278380
2018 Reversible Protein Adsorption on Mixed PEO/PAA Polymer Brushes: Role of Ionic Strength and PEO Content. Langmuir : the ACS journal of surfaces and colloids 22 29406751
2013 The overexpression of Twinkle helicase ameliorates the progression of cardiac fibrosis and heart failure in pressure overload model in mice. PloS one 22 23840758
2012 Modeling pathogenic mutations of human twinkle in Drosophila suggests an apoptosis role in response to mitochondrial defects. PloS one 22 22952820
2016 Biochemical Characterization of the Human Mitochondrial Replicative Twinkle Helicase: SUBSTRATE SPECIFICITY, DNA BRANCH MIGRATION, AND ABILITY TO OVERCOME BLOCKADES TO DNA UNWINDING. The Journal of biological chemistry 21 27226550
2015 Immunotoxicity and genotoxicity testing of PLGA-PEO nanoparticles in human blood cell model. Nanotoxicology 21 23859252
2006 A new POLG1 mutation with peo and severe axonal and demyelinating sensory-motor neuropathy. Journal of neurology 21 16715201
2019 PEO coatings design for Mg-Ca alloy for cardiovascular stent and bone regeneration applications. Materials science & engineering. C, Materials for biological applications 20 31546411
2016 PEO-generated Surfaces Support Attachment and Growth of Cells In Vitro with No Additional Benefit for Micro-roughness in Sa (0.2-4 μm). In vivo (Athens, Greece) 20 26709125
2015 The Analysis of Pendolino (peo) Mutants Reveals Differences in the Fusigenic Potential among Drosophila Telomeres. PLoS genetics 20 26110638
2012 Relationship between the affinity of PEO-PPO-PEO block copolymers for biological membranes and their cellular effects. Pharmaceutical research 20 22392332
2019 Structural basis for adPEO-causing mutations in the mitochondrial TWINKLE helicase. Human molecular genetics 19 30496414
2010 TWINKLE gene mutation: report of a French family with an autosomal dominant progressive external ophthalmoplegia and literature review. European journal of neurology 19 20880070
2019 Influence of Cholesterol and Bilayer Curvature on the Interaction of PPO-PEO Block Copolymers with Liposomes. Langmuir : the ACS journal of surfaces and colloids 18 31117745
2019 Broadening the phenotype of the TWNK gene associated Perrault syndrome. BMC medical genetics 18 31852434
2014 Adult-onset Mendelian PEO Associated with Mitochondrial Disease. Journal of neuromuscular diseases 18 27858775
2022 Performance of PEO/Polymer Coatings on the Biodegradability, Antibacterial Effect and Biocompatibility of Mg-Based Materials. Journal of functional biomaterials 17 36547527
2021 Formulation, Solubilization, and In Vitro Characterization of Quercetin-Incorporated Mixed Micelles of PEO-PPO-PEO Block Copolymers. Applied biochemistry and biotechnology 17 34611857
2016 Protein resistance efficacy of PEO-silane amphiphiles: Dependence on PEO-segment length and concentration. Acta biomaterialia 17 27090588
2022 Structural insight and characterization of human Twinkle helicase in mitochondrial disease. Proceedings of the National Academy of Sciences of the United States of America 16 35914129
2020 Spatial Distribution of PEO-PPO-PEO Block Copolymer and PEO Homopolymer in Lipid Bilayers. Langmuir : the ACS journal of surfaces and colloids 16 32216370
2015 Ultraporous nanofeatured PCL-PEO microfibrous scaffolds enhance cell infiltration, colonization and myofibroblastic differentiation. Nanoscale 16 26308365
2014 Protein adsorption can be reversibly switched on and off on mixed PEO/PAA brushes. Acta biomaterialia 16 25234158
2013 Synthesis and evaluation of 18F-FE-PEO in rodents: an 18F-labeled full agonist for opioid receptor imaging. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 16 23297076
2024 Initial SEI formation in LiBOB-, LiDFOB- and LiBF4-containing PEO electrolytes. Journal of materials chemistry. A 15 38633215
2020 Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase. The Journal of biological chemistry 15 32213598
2017 Integrated antimicrobial and antifouling ultrafiltration membrane by surface grafting PEO and N-chloramine functional groups. Journal of colloid and interface science 15 28431257
2015 Polyethylene Oxide (PEO) and Polyethylene Glycol (PEG) Polymer Sieving Matrix for RNA Capillary Electrophoresis. PloS one 15 25933347

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