Affinage

UNG

Uracil-DNA glycosylase · UniProt P13051

Length
313 aa
Mass
34.6 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UNG is the major cellular uracil-DNA glycosylase, initiating base excision repair by flipping uracil out of the DNA helix into a tight active-site pocket and excising it (PMID:7819187). The active-site geometry strictly dictates uracil specificity: substitutions in the uracil-binding pocket redirect the enzyme to excise thymine or cytosine, generating cytotoxic abasic sites (PMID:11554311), and catalysis proceeds through closure of two independently moving structural domains upon binding uracil-containing DNA (PMID:12136137). A single gene produces two isoforms by alternative splicing and dual promoters: mitochondrial UNG1 and nuclear UNG2, whose unique N-terminal extensions act as exclusive targeting signals (PMID:9016624); correct subcellular targeting is functionally essential, as a patient mutation that mistargets nuclear UNG to mitochondria abolishes its role in antibody diversification (PMID:15967827). In the nucleus, UNG2 is tethered to replication foci through PCNA and RPA interactions in its unique N-terminus, where its principal role is removal of misincorporated dUMP from newly replicated DNA rather than repair of cytosine-deamination U:G mispairs (PMID:10912000, PMID:11554311). At immunoglobulin loci, UNG processes AID-generated dU:dG lesions into abasic sites that yield the staggered double-strand breaks required for class-switch recombination and that shape the somatic hypermutation spectrum; loss of UNG shifts hypermutation toward transitions and impairs class switching (PMID:12401169, PMID:16103411). Recruitment to switch regions is guided by the scaffolding function of the translesion polymerase Rev1 (PMID:23140944) and by an RPA interaction—mediated by the RPA2 winged-helix domain and modulated by UNG ubiquitination and phosphorylation—that directs UNG to single-stranded DNA for recombinogenic processing while being dispensable for canonical double-stranded BER (PMID:33784377, PMID:38000394). Mitochondrial UNG1 is matured by mitochondrial processing peptidase (PMID:9776759), sequestered from single-stranded DNA by mtSSB during replication (PMID:22153281), and stabilized against oxidative degradation through a disulfide-bonded interaction with PRDX3 (PMID:27480846). UNG also contributes to Tet-mediated active DNA demethylation (PMID:26620559) and is the dominant glycosylase removing the chemotherapeutic 5-fluorouracil from DNA (PMID:21745813). UNG is exploited and antagonized by pathogens: HIV-1 Vpr targets UNG for proteasomal degradation via a Cul1/Cul4 E3 ligase complex (PMID:16103149). Mutations in UNG cause a hyper-IgM immunodeficiency through defective antibody diversification (PMID:15967827).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 High

    Establishing how the bacteriophage Ugi inhibitor inactivates Ung defined the enzyme's nucleic-acid-binding mode and provided the first kinetic mechanism of UDG inactivation.

    Evidence Stopped-flow kinetics and fluorescence titration of E. coli Ung with Ugi inhibitor

    PMID:8262921

    Open questions at the time
    • Mechanism characterized for the E. coli ortholog, not human UNG
    • Does not address physiological substrate engagement on chromatin
  2. 1995 High

    Recombinant characterization established UNG as the dominant cellular uracil-DNA glycosylase with a preference for single-stranded DNA, answering which enzyme accounts for bulk UDG activity.

    Evidence Recombinant expression, kinetic assays on ss/dsDNA, immunofluorescence, antibody inhibition of HeLa extracts

    PMID:7819187

    Open questions at the time
    • Did not resolve whether the primary in vivo role is replicative dUMP removal versus deamination repair
    • Isoform contributions not separated
  3. 1997 High

    Discovery of two isoforms with distinct N-terminal targeting signals answered how one gene partitions uracil repair between nucleus and mitochondria.

    Evidence Alternative splicing analysis and GFP-fusion localization in HeLa cells

    PMID:9016624

    Open questions at the time
    • Functional division of labor between isoforms not yet defined
    • No partner proteins identified
  4. 1998 High

    Mapping mitochondrial UNG1 maturation defined how the imported preform is processed to active forms, and structural work showed the catalytic mechanism is conserved across kingdoms.

    Evidence In vitro mitochondrial processing with peptide sequencing; X-ray crystallography of E. coli UDG-Ugi at 3.2 Å

    PMID:9776748 PMID:9776759

    Open questions at the time
    • Identity of the second EDTA-stimulated protease unresolved
    • Crystallographic mechanism from ortholog, not human UNG
  5. 2000 High

    Knockout mice resolved that nuclear UNG's primary role is removing misincorporated dUMP during replication rather than repairing deamination-derived U:G mispairs, with SMUG1 as backup.

    Evidence Ung-/- mice with genomic uracil measurement and activity assays on isolated nuclei and extracts

    PMID:10912000

    Open questions at the time
    • Did not explain how UNG is recruited to replication sites
    • Immunological role not yet examined
  6. 2001 Medium

    Identifying PCNA and RPA interactions with the UNG2 N-terminus explained how the nuclear isoform is physically tethered to the replication machinery, and active-site mutagenesis defined the basis of uracil specificity.

    Evidence Co-localization in replication foci, N-terminal interaction constructs, active-site mutagenesis with E. coli functional assays

    PMID:11554311

    Open questions at the time
    • Interaction data from a single lab in a review-format paper
    • Relative contributions of PCNA versus RPA tethering not dissected
  7. 2002 High

    Knockout immunology established UNG as the major glycosylase processing AID-induced dU:dG lesions, linking it to class-switch recombination and the somatic hypermutation spectrum.

    Evidence Ung-/- mice with Ig mutation spectrum analysis and CSR assays; complemented by crystallographic domain-closure analysis of UDG

    PMID:12136137 PMID:12401169

    Open questions at the time
    • Mechanism of UNG recruitment to switch regions unknown
    • How abasic sites are converted to DSBs not yet shown
  8. 2005 High

    Linking UNG-generated abasic sites to staggered DSBs at AID hotspots, and human patient mutations to defective uracil removal, established the requirement for nuclear-localized UNG in antibody diversification and revealed pathogen exploitation by HIV-1 Vpr.

    Evidence LM-PCR of switch-region DSBs in ung-/- and AID-/- B cells; patient UNG mutation analysis with subcellular fractionation; Vpr Co-IP with Cul1/Cul4 and virion activity assays

    PMID:15967827 PMID:16103149 PMID:16103411

    Open questions at the time
    • Recruitment factors directing UNG to switch regions still unidentified
    • Vpr findings from single-lab Co-IP without structural detail
  9. 2011 High

    Defining UNG as the dominant 5-fluorouracil-DNA glycosylase and characterizing mtSSB sequestration of UNG1 clarified UNG's roles in drug response and mitochondrial replication regulation.

    Evidence siRNA knockdown with FU-DNA repair and viability assays; in vitro uracil excision and AP-nicking assays with purified UNG1 and mtSSB

    PMID:21745813 PMID:22153281

    Open questions at the time
    • FU cytotoxicity shown to be RNA-mediated, leaving DNA repair role uncoupled from sensitivity
    • mtSSB-UNG1 interaction characterized only in vitro
  10. 2012 High

    Identifying Rev1 as a scaffold recruiting UNG to switch regions answered how UNG is targeted to Ig loci independent of its own catalytic activity.

    Evidence Reciprocal Co-IP, ChIP of UNG at switch regions, CSR rescue with catalytically inactive Rev1 in Rev1-/- B cells

    PMID:23140944

    Open questions at the time
    • Whether Rev1 and RPA act in the same or parallel recruitment pathways unresolved
    • Single-lab study
  11. 2016 Medium

    UNG was placed in additional contexts—Tet-mediated active DNA demethylation, protection of AID-targeted telomeres, and PRDX3-dependent stabilization in mitochondria under oxidative stress.

    Evidence Methylated reporter and 5caC assays with Tet2; telomere integrity and germinal-center analyses in Ung-/- B cells; UNG1-PRDX3 proteomics and Co-IP with LonP1-dependence assays

    PMID:26620559 PMID:27480846 PMID:27697833

    Open questions at the time
    • Demethylation role only partially mechanistically defined
    • Telomere protection mechanism inferred from comparison to MMR pathway
    • PRDX3 disulfide interaction from a single lab
  12. 2019 Medium

    Discovery of a nuclear-targeted UNG1 variant lacking the PCNA motif but retaining RPA binding revealed a second UNG species acting on ssDNA in transcribed Ig regions and ahead of replication forks.

    Evidence Isoform-specific mouse and human cell lines, CSR assays, genomic uracil measurement, motif analysis

    PMID:30838409

    Open questions at the time
    • Relative in vivo contribution of nuclear UNG1 versus UNG2 not quantified
    • Single-lab study
  13. 2021 High

    Structural and biochemical dissection of the UNG-RPA interaction defined how UNG is licensed to excise uracil from RPA-coated ssDNA and how PTMs tune this activity.

    Evidence In vitro excision on RPA-ssDNA, NMR of the RPA2 winged-helix interaction, mutagenesis, and ubiquitination/phosphorylation analysis

    PMID:33784377

    Open questions at the time
    • Enzymes setting the activating ubiquitination and inhibitory phosphorylations not identified
    • In-cell consequences of the interaction not yet tested
  14. 2024 High

    Targeted disruption of the UNG RPA-binding motif epistatically separated UNG's ssDNA recombinogenic role at Ig loci from its bulk dsDNA repair function.

    Evidence B-cell clones with RPA-binding-motif mutations, CSR and Sμ mutation-frequency assays, genomic uracil measurement across seven Ung genotypes

    PMID:38000394

    Open questions at the time
    • How RPA and Rev1 recruitment pathways are coordinated remains open
    • Structural state of UNG on RPA-ssDNA in vivo not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown which kinases and ubiquitin ligases dynamically control UNG's RPA-dependent targeting, and how the multiple recruitment routes (PCNA, RPA, Rev1) are integrated across replication, transcription, and immunoglobulin diversification.
  • Identity of UNG-modifying enzymes unknown
  • Integration of competing recruitment pathways unresolved
  • In-cell structural state of UNG complexes uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 5 GO:0003677 DNA binding 2 GO:0016787 hydrolase activity 2
Localization
GO:0005739 mitochondrion 4 GO:0005634 nucleus 3
Pathway
R-HSA-168256 Immune System 5 R-HSA-73894 DNA Repair 3
Partners
PCNAPRDX3REV1RPASSBP1TET2VPR

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 The UNG gene encodes two distinct isoforms via alternative splicing and use of different promoters: UNG1 (304 aa, mitochondrial targeting sequence) and UNG2 (313 aa, nuclear targeting sequence). GFP fusion experiments in HeLa cells demonstrated that the unique N-terminal 35 residues of UNG1 direct the protein exclusively to mitochondria, while the unique N-terminal 44 residues of UNG2 direct it exclusively to the nucleus. Both isoforms are catalytically active. Alternative splicing analysis, coupled transcription/translation in rabbit reticulocyte lysates, GFP-fusion constructs with transient transfection in HeLa cells and fluorescence microscopy Nucleic Acids Research High 9016624
1995 Recombinant human UNG (UNG-delta84) is a uracil-DNA glycosylase that removes uracil from both single-stranded and double-stranded DNA, preferring ssDNA (~3-fold faster). It displays sequence-context specificity for uracil removal from UA and UG base pairs in dsDNA, with UG mispairs (simulating deaminated cytosine) generally removed slightly faster. Immunofluorescence with polyclonal antibodies showed the major fraction of UNG in the nucleus, and >98% of total UDG activity in HeLa extracts was inhibited by anti-UNG antibodies, establishing UNG as the major cellular uracil-DNA glycosylase. Recombinant protein expression and purification in E. coli, in vitro enzymatic assays with ssDNA and dsDNA substrates, kinetic analysis, immunofluorescence, antibody inhibition of cell extracts Biochemistry High 7819187
1998 Mitochondrial UNG1 preform is processed to two distinct forms after import: a major form lacking 29 N-terminal residues (UNG1Δ29, 31 kDa) and minor forms lacking 75/77 residues (26 kDa). The cleavage is mediated by mitochondrial processing peptidase (MPP) at the first site, and a distinct, EDTA-stimulated protease (not MPP) at the second site. UNG1Δ29 retains full uracil-DNA glycosylase activity but, unlike other UDGs, is not inhibited by AP sites. Expression in insect cells, in vitro processing by human mitochondrial extracts, peptide sequencing of cleavage sites, enzymatic activity assays Nucleic Acids Research High 9776759
2000 UNG knockout mice show slow removal of uracil from misincorporated dUMP in isolated nuclei and an elevated steady-state level of uracil in DNA in dividing cells (~2000 uracil residues/cell), establishing that the primary role of nuclear UNG is removal of misincorporated dUMP during DNA replication rather than repair of U:G mispairs from cytosine deamination. A backup activity with properties of SMUG1 handles U:G mispairs in UNG-null tissue extracts. Gene-targeted knockout mice, uracil measurement in DNA from ung-/- cells, enzymatic assays on isolated nuclei and tissue extracts Molecular Cell High 10912000
2001 PCNA and RPA co-localize with UNG2 in replication foci and physically interact with N-terminal sequences unique to UNG2 (not present in UNG1), tethering UNG2 to the replication machinery. Mitochondrial UNG1 is processed by MPP and a second unidentified protease. Active-site substitutions in the catalytic domain generate variants that remove thymine or cytosine instead of uracil, inducing cytotoxic AP sites in E. coli, demonstrating the importance of the uracil-binding pocket geometry. Co-localization by immunofluorescence, interaction studies with N-terminal domain constructs, active-site mutagenesis, functional assays in E. coli Progress in Nucleic Acid Research and Molecular Biology Medium 11554311
2002 UNG deficiency in mice substantially inhibits immunoglobulin class-switch recombination and distorts the somatic hypermutation pattern: in ung-/- animals, mutations at dC/dG pairs shift dramatically toward transitions (95%), indicating loss of abasic site formation. The pattern of mutations at dA/dT pairs is unaffected. These results establish UNG as the major DNA glycosylase processing AID-induced dU/dG lesions at immunoglobulin loci. Gene-targeted ung-/- mice, mutation spectrum analysis of immunoglobulin genes by sequencing, class-switch recombination assays Current Biology High 12401169
2005 HIV-1 Vpr binds to UNG and to SMUG1 and induces their proteasomal degradation via an E3 ubiquitin ligase complex containing Cul1 and Cul4. This reduces virion-associated uracil-DNA glycosylase activity. Vpr(+) HIV-1 replicated more efficiently than Vpr(-) virus in the presence of limited APOBEC3G, suggesting Vpr degrades UNG to reduce abasic sites in viral reverse transcripts from APOBEC3-mediated deamination. Co-immunoprecipitation of Vpr with Cul1/Cul4, western blot of UNG in virions, enzymatic activity assays of virion extracts, viral replication assays with APOBEC3G Journal of Virology Medium 16103149
2005 UNG-dependent double-strand breaks (DSBs) in immunoglobulin switch regions occur preferentially at G:C base pairs in WRC/GYW AID hotspots, as detected by ligation-mediated PCR. DSB kinetics correlate with AID expression, and DSBs are absent in AID- and UNG-deficient B cells, indicating that staggered breaks are processed from AID-initiated single-strand breaks via UNG-generated abasic sites. Ligation-mediated PCR to detect DSBs in switch regions of splenic B cells, analysis of ung-/- and AID-/- cells Journal of Experimental Medicine High 16103411
2005 B cells from hyper-IgM patients carrying UNG mutations cannot efficiently remove uracil from single-stranded DNA, and SMUG1 cannot compensate for this nuclear UNG2 deficiency. One patient UNG mutation (F251S) creates a protein that is fully active when expressed in E. coli but is mistargeted to mitochondria and degraded in mammalian cells, demonstrating that nuclear localization of UNG2 is required for its function in antibody diversification. Uracil excision assays on ssDNA using B-cell extracts, expression of mutant UNG in E. coli and mammalian cells, subcellular fractionation, genomic uracil measurement Journal of Experimental Medicine High 15967827
2011 UNG-initiated base excision repair is the major route for 5-fluorouracil (FU) removal from DNA in human cancer cells: UNG accounts for >90% of FU-DNA repair in vitro and in vivo, with SMUG1, TDG, and MBD4 contributing modestly. However, knockdown of UNG or other UDGs did not affect sensitivity to FU, because FU cytotoxicity is predominantly RNA-mediated (cells accumulate ~3000–15,000-fold more FU in RNA than DNA). siRNA knockdown of individual UDGs, in vitro and in vivo FU-DNA repair assays, cell viability assays, ribonucleoside rescue experiments Nucleic Acids Research High 21745813
2011 Mitochondrial single-strand DNA binding protein (mtSSB) inhibits uracil excision from single-stranded DNA by UNG1 and also inhibits AP site nicking by APE1 in ssDNA. A surface motif in mtSSB can recruit UNG1 to DNA-bound mtSSB. This suggests mtSSB sequesters UNG1 to prevent nicking of ssDNA during mtDNA replication and facilitates rapid repair once dsDNA is restored. In vitro uracil excision assays with purified UNG1 and mtSSB, AP site nicking assays, protein interaction studies identifying mtSSB surface motif DNA Repair Medium 22153281
2012 The translesion synthesis polymerase Rev1 directly interacts with UNG and recruits it to immunoglobulin switch regions in an AID-dependent, UNG-independent manner. Rev1-deficient B cells show reduced UNG recruitment to switch regions, reduced dU glycosylation, and reduced class-switch recombination. Rescue of CSR by catalytically inactive Rev1 demonstrates that Rev1's scaffolding function (not its enzymatic activity) is required for UNG recruitment. Co-immunoprecipitation of Rev1 and UNG, ChIP to detect UNG at switch regions, CSR assays in Rev1-/- B cells, complementation with catalytically inactive Rev1 mutant Cell Reports High 23140944
2015 UNG2 reduces genomic DNA methylation and activates transcription of a methylation-silenced reporter when co-transfected with Tet2 in HEK293T cells. UNG2 decreases 5-carboxylcytosine (5caC) levels from genomic DNA and reporter plasmids, similar to TDG. Ung deficiency partially impairs DNA demethylation in mouse zygotes, indicating UNG participates in Tet-mediated active DNA demethylation. Methylated luciferase reporter assay, genomic 5caC measurement, co-transfection of UNG2 with Tet2 in HEK293T cells, analysis of Ung-/- mouse zygotes Journal of Biological Chemistry Medium 26620559
2016 Telomeres are off-target substrates of AID in B cells. UNG activity protects B cells from AID-induced telomere loss: in the absence of UNG, mismatch repair processes G:U lesions at telomeres in a deleterious manner, causing telomere loss and defective cell proliferation. UNG deficiency reduces germinal center B cell clonal expansion in mice and blocks proliferation of tumor B cells expressing AID. Analysis of telomere integrity in UNG-deficient B cells, germinal center analysis in Ung-/- mice, proliferation assays in tumor B cells with AID expression Journal of Experimental Medicine Medium 27697833
2016 Under oxidative stress, UNG1 interacts with Peroxiredoxin 3 (PRDX3) via a disulfide bond in mitochondria, and this interaction protects UNG1 from ROS-mediated degradation by Lon protease 1 (LonP1). Knockdown of PRDX3 aggravates ROS-mediated UNG1 degradation. UNG1 overexpression enhances cellular resistance to oxidative stress and protects mitochondrial DNA from oxidation. Proteomics/mass spectrometry of UNG1-binding partners, co-immunoprecipitation under oxidative stress, PRDX3 knockdown, LonP1 dependence assays, mtDNA oxidation measurement Free Radical Biology and Medicine Medium 27480846
2019 A distinct UNG1 isoform variant is targeted to the cell nucleus (in addition to mitochondria) where it supports antibody class-switch recombination and repairs genomic uracil. Unlike UNG2, this nuclear UNG1 variant lacks a PCNA-binding motif but retains an RPA-binding ability, suggesting it acts on ssDNA in transcribed antibody gene regions and ahead of replication forks. Generation of isoform-specific mouse and human cell lines, CSR assays, genomic uracil measurement, subcellular fractionation, analysis of PCNA and RPA binding motifs Nucleic Acids Research Medium 30838409
2021 UNG (but not SMUG1) efficiently excises uracil from RPA-coated ssDNA, and this depends on a functional interaction between the flexible winged-helix (WH) domain of RPA2 and the N-terminal RPA-binding helix in UNG. This interaction is promoted by mono-ubiquitination of UNG and diminished by cell-cycle-regulated phosphorylations on UNG. In vitro uracil excision assays on RPA-coated ssDNA, NMR structural analysis of RPA2-WH domain interaction, mutagenesis of UNG RPA-binding helix, analysis of ubiquitination and phosphorylation effects Nucleic Acids Research High 33784377
2024 The UNG:RPA interaction plays a crucial role in class-switch recombination and repair of AID-induced uracil at the Ig loci in B cells, but does not significantly affect total genomic uracil levels. This was established by generating B-cell clones with targeted mutations in the UNG RPA-binding motif, demonstrating that RPA guides UNG to ssDNA for mutagenic/recombinogenic processing but is dispensable for post-replicative and canonical BER in dsDNA. Targeted mutations in UNG RPA-binding motif in B-cell clones, CSR assays, Ig Sμ mutation frequency analysis, genomic uracil measurement across seven Ung genotypes Nucleic Acids Research High 38000394
1993 E. coli Ung forms an extremely stable 1:1 protein complex with bacteriophage PBS2 Ugi inhibitor via a two-step mechanism: a rapid pre-equilibrium (Kd = 1.3 µM) followed by an irreversible second step (rate constant 195 s⁻¹). Once in the Ung·Ugi complex, Ung can no longer bind nucleic acids, and free Ugi cannot exchange with bound Ugi, demonstrating the mechanism of Ugi-mediated inactivation. Fluorescence labeling of Ung, stopped-flow kinetic analysis, fluorescence quenching titration, nucleic acid binding competition assays Journal of Biological Chemistry High 8262921
2006 E. coli nucleoside-diphosphate kinase (Ndk) directly and specifically interacts with Ung, stimulating Ung's catalytic activity. Co-purification and co-immunoprecipitation from cell extracts, plus GST pulldown and far-Western with purified proteins, demonstrate the interaction is direct and occurs in a cellular context. This is the first identified protein-protein interaction partner for E. coli Ung. Multi-column co-purification, co-immunoprecipitation from cellular extracts, GST pulldown with purified proteins, far-Western analysis, enzymatic activity assays Journal of Biological Chemistry Medium 16895920
2004 Electrostatic surface potential optimization is a strategy for cold adaptation of UNG: substitution of residues altering the surface charge near the active site of cod UNG reduces activity and increases stability, demonstrating the importance of surface electrostatics for catalytic efficiency at low temperatures. Crystal structures of single mutants (V171E and E171V) confirmed the structural basis. Site-directed mutagenesis of cod and human UNG, enzymatic activity assays, crystal structure determination of mutants Journal of Molecular Biology Medium 15491608
1998 The crystal structure of E. coli UDG in complex with Ugi at 3.2 Å resolution was determined, revealing structural similarity to human and viral UDGs despite sequence differences. The active site residues involved in DNA binding are spatially conserved, indicating the same catalytic mechanism across prokaryotic and eukaryotic UDGs. Structural comparison delineated constant versus variable regions of the UDG molecule. X-ray crystallography at 3.2 Å resolution, structural comparison with human and viral UDG structures, mutational analysis Nucleic Acids Research Medium 9776748
2002 Domain closure is a key mechanistic feature of UDG action: crystal structures of free E. coli UDG and its complexes with Ugi show the enzyme comprises two independently moving structural domains that close upon binding uracil-containing DNA but not upon binding Ugi protein. This domain movement underlies the extrahelical uracil recognition mechanism. X-ray crystallography of multiple crystal forms of free E. coli UDG and Ugi complexes, comparative structural analysis with human UDG structures Acta Crystallographica Section D Medium 12136137

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Immunoglobulin isotype switching is inhibited and somatic hypermutation perturbed in UNG-deficient mice. Current biology : CB 548 12401169
2000 Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication. Molecular cell 278 10912000
1997 Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene. Nucleic acids research 261 9016624
1995 Properties of a recombinant human uracil-DNA glycosylase from the UNG gene and evidence that UNG encodes the major uracil-DNA glycosylase. Biochemistry 250 7819187
2005 Human immunodeficiency virus type 1 Vpr induces the degradation of the UNG and SMUG uracil-DNA glycosylases. Journal of virology 185 16103149
1982 Specific mutator effects of ung (uracil-DNA glycosylase) mutations in Escherichia coli. Journal of bacteriology 170 7047496
2014 Simultaneous elimination of carryover contamination and detection of DNA with uracil-DNA-glycosylase-supplemented loop-mediated isothermal amplification (UDG-LAMP). Chemical communications (Cambridge, England) 152 24577617
2005 Inducible DNA breaks in Ig S regions are dependent on AID and UNG. The Journal of experimental medicine 143 16103411
2006 The in vivo pattern of AID targeting to immunoglobulin switch regions deduced from mutation spectra in msh2-/- ung-/- mice. The Journal of experimental medicine 142 16894013
2003 Gene-targeted mice lacking the Ung uracil-DNA glycosylase develop B-cell lymphomas. Oncogene 118 12934097
1988 Sequence analysis, expression, and conservation of Escherichia coli uracil DNA glycosylase and its gene (ung). The Journal of biological chemistry 110 2836397
2011 UNG-initiated base excision repair is the major repair route for 5-fluorouracil in DNA, but 5-fluorouracil cytotoxicity depends mainly on RNA incorporation. Nucleic acids research 100 21745813
2005 C --> T mutagenesis and gamma-radiation sensitivity due to deficiency in the Smug1 and Ung DNA glycosylases. The EMBO journal 100 15902269
2006 Somatic hypermutation and class switch recombination in Msh6(-/-)Ung(-/-) double-knockout mice. Journal of immunology (Baltimore, Md. : 1950) 97 17015724
2005 B cells from hyper-IgM patients carrying UNG mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil. The Journal of experimental medicine 89 15967827
2012 Germline ablation of SMUG1 DNA glycosylase causes loss of 5-hydroxymethyluracil- and UNG-backup uracil-excision activities and increases cancer predisposition of Ung-/-Msh2-/- mice. Nucleic acids research 86 22447450
2001 Properties and functions of human uracil-DNA glycosylase from the UNG gene. Progress in nucleic acid research and molecular biology 75 11554311
2006 Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition. BMC cancer 68 17029639
2005 MRE11/RAD50 cleaves DNA in the AID/UNG-dependent pathway of immunoglobulin gene diversification. Molecular cell 64 16285919
2002 Substrate recognition by a family of uracil-DNA glycosylases: UNG, MUG, and TDG. Chemical research in toxicology 61 12184783
2005 Uracil-directed ligand tethering: an efficient strategy for uracil DNA glycosylase (UNG) inhibitor development. Journal of the American Chemical Society 60 16332091
1993 Kinetics of the uracil-DNA glycosylase/inhibitor protein association. Ung interaction with Ugi, nucleic acids, and uracil compounds. The Journal of biological chemistry 59 8262921
2002 Immunoglobulin genes: generating diversity with AID and UNG. Current biology : CB 56 12419200
1998 X-ray analysis of a complex of Escherichia coli uracil DNA glycosylase (EcUDG) with a proteinaceous inhibitor. The structure elucidation of a prokaryotic UDG. Nucleic acids research 53 9776748
1998 Human mitochondrial uracil-DNA glycosylase preform (UNG1) is processed to two forms one of which is resistant to inhibition by AP sites. Nucleic acids research 51 9776759
1987 Asymmetric cytosine deamination revealed by spontaneous mutational specificity in an Ung- strain of Escherichia coli. Molecular & general genetics : MGG 50 3312959
2005 The mutation spectrum of purified AID is similar to the mutability index in Ramos cells and in ung(-/-)msh2(-/-) mice. Immunogenetics 49 15650878
2006 Quantitative determination of uracil residues in Escherichia coli DNA: Contribution of ung, dug, and dut genes to uracil avoidance. DNA repair 48 16908222
1981 Thermal resistance to photoreactivation of specific mutations potentiated in E. coli B/r ung by ultraviolet light. Molecular & general genetics : MGG 48 7022139
2017 Uracil Accumulation and Mutagenesis Dominated by Cytosine Deamination in CpG Dinucleotides in Mice Lacking UNG and SMUG1. Scientific reports 47 28775312
2016 Advanced uracil DNA glycosylase-supplemented real-time reverse transcription loop-mediated isothermal amplification (UDG-rRT-LAMP) method for universal and specific detection of Tembusu virus. Scientific reports 46 27270462
1992 Use of modified nucleotides and uracil-DNA glycosylase (UNG) for the control of contamination in the PCR-based amplification of RNA. Molecular and cellular probes 45 1406734
2014 Uracil DNA glycosylase (UNG) loss enhances DNA double strand break formation in human cancer cells exposed to pemetrexed. Cell death & disease 43 24503537
2011 Prehospital intubation of the moderately injured patient: a cause of morbidity? A matched-pairs analysis of 1,200 patients from the DGU Trauma Registry. Critical care (London, England) 43 21914175
2015 Genomically Incorporated 5-Fluorouracil that Escapes UNG-Initiated Base Excision Repair Blocks DNA Replication and Activates Homologous Recombination. Molecular pharmacology 42 26494862
1985 Isolation of insertion, deletion, and nonsense mutations of the uracil-DNA glycosylase (ung) gene of Escherichia coli K-12. Journal of bacteriology 41 2997126
2012 Rev1 recruits ung to switch regions and enhances du glycosylation for immunoglobulin class switch DNA recombination. Cell reports 39 23140944
2005 Minimizing DNA contamination by using UNG-coupled quantitative real-time PCR on degraded DNA samples: application to ancient DNA studies. BioTechniques 39 15884675
2021 Smart Catalyzed Hairpin Assembly-Induced DNAzyme Nanosystem for Intracellular UDG Imaging. Analytical chemistry 38 34583508
2009 The concerted action of Msh2 and UNG stimulates somatic hypermutation at A . T base pairs. Molecular and cellular biology 38 19596785
2012 UNG shapes the specificity of AID-induced somatic hypermutation. The Journal of experimental medicine 36 22665573
1993 Generation of cohesive ends on PCR products by UDG-mediated excision of dU, and application for cloning into restriction digest-linearized vectors. PCR methods and applications 34 8324507
1993 A novel method employing UNG to avoid carry-over contamination in RNA-PCR. Nucleic acids research 33 8367319
1991 Human uracil-DNA glycosylase complements E. coli ung mutants. Nucleic acids research 33 1886771
2000 Analysis of uracil-DNA glycosylases from the murine Ung gene reveals differential expression in tissues and in embryonic development and a subcellular sorting pattern that differs from the human homologues. Nucleic acids research 32 10871356
2019 [Geriatric Trauma Center DGU®: Evaluation of clinical and economic parameters : A pilot study in a german university hospital]. Der Unfallchirurg 31 29675629
2003 Expression of uracil DNA glycosylase (UDG) does not affect cellular sensitivity to thymidylate synthase (TS) inhibition. European journal of cancer (Oxford, England : 1990) 31 12565992
1998 Expression of a uracil DNA glycosylase (UNG) inhibitor in mammalian cells: varicella-zoster virus can replicate in vitro in the absence of detectable UNG activity. Virology 31 9837803
2013 Separation of function between isotype switching and affinity maturation in vivo during acute immune responses and circulating autoantibodies in UNG-deficient mice. Journal of immunology (Baltimore, Md. : 1950) 30 23667108
2009 Synergistic effects of UdgB and Ung in mutation prevention and protection against commonly encountered DNA damaging agents in Mycobacterium smegmatis. Microbiology (Reading, England) 29 19942658
1995 The DNA repair genes RAD54 and UNG1 are cell cycle regulated in budding yeast but MCB promoter elements have no essential role in the DNA damage response. Nucleic acids research 29 7610042
2015 Uracil-DNA Glycosylase UNG Promotes Tet-mediated DNA Demethylation. The Journal of biological chemistry 28 26620559
2019 Genetic Polymorphisms Predisposing the Interleukin 6-Induced APOBEC3B-UNG Imbalance Increase HCC Risk via Promoting the Generation of APOBEC-Signature HBV Mutations. Clinical cancer research : an official journal of the American Association for Cancer Research 27 31152021
2016 UNG protects B cells from AID-induced telomere loss. The Journal of experimental medicine 27 27697833
1986 Thermal resistance of UV-mutagenesis to photoreactivation in E. coli B/r uvrA ung: estimate of activation energy and further analysis. Molecular & general genetics : MGG 27 3531774
2019 Uracil-DNA glycosylase UNG1 isoform variant supports class switch recombination and repairs nuclear genomic uracil. Nucleic acids research 26 30838409
2008 Insights from xanthine and uracil DNA glycosylase activities of bacterial and human SMUG1: switching SMUG1 to UDG. Journal of molecular biology 26 18835277
2004 Optimisation of the surface electrostatics as a strategy for cold adaptation of uracil-DNA N-glycosylase (UNG) from Atlantic cod (Gadus morhua). Journal of molecular biology 26 15491608
2005 Structure of the uracil-DNA N-glycosylase (UNG) from Deinococcus radiodurans. Acta crystallographica. Section D, Biological crystallography 24 16041069
2008 AID- and Ung-dependent generation of staggered double-strand DNA breaks in immunoglobulin class switch DNA recombination: a post-cleavage role for AID. Molecular immunology 22 18760480
2016 Hydrogen peroxide mediated mitochondrial UNG1-PRDX3 interaction and UNG1 degradation. Free radical biology & medicine 21 27480846
2013 Monitoring eukaryotic and bacterial UDG repair activity with DNA-multifluorophore sensors. Nucleic acids research 21 23644286
1986 Differential enhancement of spontaneous transition mutations in the lacI gene of an Ung- strain of Escherichia coli. Mutation research 21 3531843
2012 SMUG1 but not UNG DNA glycosylase contributes to the cellular response to recovery from 5-fluorouracil induced replication stress. Mutation research 20 23253900
2006 Molecular and functional interactions between Escherichia coli nucleoside-diphosphate kinase and the uracil-DNA glycosylase Ung. The Journal of biological chemistry 19 16895920
2001 Sequence variation in the human uracil-DNA glycosylase (UNG) gene. Mutation research 19 11104908
1998 Use of a coupled transcriptional system for consistent overexpression and purification of UDG-Ugi complex and Ugi from Escherichia coli. Protein expression and purification 19 9675057
2019 Comparison of the RE-529 sequence and B1 gene for Toxoplasma gondii detection in blood samples of the at-risk seropositive cases using uracil DNA glycosylase supplemented loop-mediated isothermal amplification (UDG-LAMP) assay. Microbial pathogenesis 18 31862390
2010 Loss of Caenorhabditis elegans UNG-1 uracil-DNA glycosylase affects apoptosis in response to DNA damaging agents. DNA repair 18 20493785
2002 Domain closure and action of uracil DNA glycosylase (UDG): structures of new crystal forms containing the Escherichia coli enzyme and a comparative study of the known structures involving UDG. Acta crystallographica. Section D, Biological crystallography 18 12136137
2019 The Influence of (5'R)- and (5'S)-5',8-Cyclo-2'-Deoxyadenosine on UDG and hAPE1 Activity. Tandem Lesions are the Base Excision Repair System's Nightmare. Cells 16 31652769
2018 Sensitive detection of uracil-DNA glycosylase (UDG) activity based on terminal deoxynucleotidyl transferase-assisted formation of fluorescent copper nanoclusters (CuNCs). Talanta 16 30625549
2021 RPA2 winged-helix domain facilitates UNG-mediated removal of uracil from ssDNA; implications for repair of mutagenic uracil at the replication fork. Nucleic acids research 15 33784377
2018 UNG-1 and APN-1 are the major enzymes to efficiently repair 5-hydroxymethyluracil DNA lesions in C. elegans. Scientific reports 15 29717169
2018 Isotype-Switched Autoantibodies Are Necessary To Facilitate Central Nervous System Autoimmune Disease in Aicda and Ung Mice. Journal of immunology (Baltimore, Md. : 1950) 15 29980612
2017 An advanced uracil DNA glycosylase-supplemented loop-mediated isothermal amplification (UDG-LAMP) technique used in the sensitive and specific detection of Cryptosporidium parvum, Cryptosporidium hominis, and Cryptosporidium meleagridis in AIDS patients. Diagnostic microbiology and infectious disease 15 29366630
2014 Somatic hypermutation at A/T-rich oligonucleotide substrates shows different strand polarities in Ung-deficient or -proficient backgrounds. Molecular and cellular biology 15 24710273
2011 mtSSB may sequester UNG1 at mitochondrial ssDNA and delay uracil processing until the dsDNA conformation is restored. DNA repair 15 22153281
2005 Mutation frequencies and AID activation state in B-cell lymphomas from Ung-deficient mice. Oncogene 15 15735713
2023 Early total care or damage control orthopaedics for major fractures ? Results of propensity score matching for early definitive versus early temporary fixation based on data from the trauma registry of the German Trauma Society (TraumaRegister DGU®). European journal of trauma and emergency surgery : official publication of the European Trauma Society 14 36662169
2009 Over-expression of SUMO-1 induces the up-regulation of heterogeneous nuclear ribonucleoprotein A2/B1 isoform B1 (hnRNP A2/B1 isoform B1) and uracil DNA glycosylase (UDG) in hepG2 cells. Cell biochemistry and function 14 19384898
2004 Negative regulation of DNA repair gene (ung) expression by the CpxR/CpxA two-component system in Escherichia coli K-12 and induction of mutations by increased expression of CpxR. Journal of bacteriology 14 15576781
2022 Colorimetric detection of SARS-CoV-2 by uracil-DNA glycosylase (UDG) reverse transcription loop-mediated isothermal amplification (RT-LAMP). International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 13 35472524
2020 The uracil-DNA glycosylase UNG protects the fitness of normal and cancer B cells expressing AID. NAR cancer 13 33554121
2011 Characterization of family IV UDG from Aeropyrum pernix and its application in hot-start PCR by family B DNA polymerase. PloS one 13 22087273
2011 Genetic polymorphisms of the DNA repair gene UNG are associated with the susceptibility of rheumatoid arthritis. Rheumatology international 13 22138674
2002 Use of heat labile UNG in an RT-PCR assay for enterovirus detection. Journal of virological methods 13 12176142
2021 A highly sensitive method for simultaneous detection of hAAG and UDG activity based on multifunctional dsDNA probes mediated exponential rolling circle amplification. Talanta 12 34074415
2017 Uracil DNA glycosylase (UDG) activities in Bradyrhizobium diazoefficiens: characterization of a new class of UDG with broad substrate specificity. Nucleic acids research 12 28369586
2010 Detrimental effects of hypoxia-specific expression of uracil DNA glycosylase (Ung) in Mycobacterium smegmatis. Journal of bacteriology 12 20971917
2024 RPA guides UNG to uracil in ssDNA to facilitate antibody class switching and repair of mutagenic uracil at the replication fork. Nucleic acids research 11 38000394
2019 A tri-functional probe mediated exponential amplification strategy for highly sensitive detection of Dnmt1 and UDG activities at single-cell level. Analytica chimica acta 11 32081181
2018 Development of uracil-DNA-glycosylase-supplemented loop-mediated isothermal amplification coupled with nanogold probe (UDG-LAMP-AuNP) for specific detection of Pseudomonas aeruginosa. Molecular medicine reports 11 29436623
2014 Opinion: uracil DNA glycosylase (UNG) plays distinct and non-canonical roles in somatic hypermutation and class switch recombination. International immunology 11 24994819
2014 Uracil-DNA glycosylase (UNG) rs246079 G/A polymorphism is associated with decreased risk of esophageal cancer in a Chinese population. Medical oncology (Northwood, London, England) 11 25301111
2011 Thermal unfolding studies of cold adapted uracil-DNA N-glycosylase (UNG) from Atlantic cod (Gadus morhua). A comparative study with human UNG. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 11 21959147
2003 hSMUG1 can functionally compensate for Ung1 in the yeast Saccharomyces cerevisiae. DNA repair 11 12547394
1997 Optimized PCR amplification of influenza A virus RNA using Tth DNA polymerase, incorporating uracil N glycosylase (UNG) in a single tube reaction. Journal of clinical laboratory analysis 11 9406050
2021 Use of a molecular beacon based fluorescent method for assaying uracil DNA glycosylase (Ung) activity and inhibitor screening. Biochemistry and biophysics reports 10 33665381
2019 A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers. Molecular oncology 10 30747491

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