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    UNG uracil DNA glycosylase [ Homo sapiens (human) ]

    Gene ID: 7374, updated on 17-Jun-2024

    GeneRIFs: Gene References Into Functions

    GeneRIFPubMed TitleDate
    Replication Protein A Enhances Kinetics of Uracil DNA Glycosylase on ssDNA and Across DNA Junctions: Explored with a DNA Repair Complex Produced with SpyCatcher/SpyTag Ligation.

    Replication Protein A Enhances Kinetics of Uracil DNA Glycosylase on ssDNA and Across DNA Junctions: Explored with a DNA Repair Complex Produced with SpyCatcher/SpyTag Ligation.
    Greenwood SN, Kulkarni RS, Mikhail M, Weiser BP., Free PMC Article

    05/30/2023
    Uracil-DNA glycosylase efficiency is modulated by substrate rigidity.

    Uracil-DNA glycosylase efficiency is modulated by substrate rigidity.
    Orndorff PB, Poddar S, Owens AM, Kumari N, Ugaz BT, Amin S, Van Horn WD, van der Vaart A, Levitus M., Free PMC Article

    03/14/2023
    FAM72A antagonizes UNG2 to promote mutagenic repair during antibody maturation.

    FAM72A antagonizes UNG2 to promote mutagenic repair during antibody maturation.
    Feng Y, Li C, Stewart JA, Barbulescu P, Seija Desivo N, Álvarez-Quilón A, Pezo RC, Perera MLW, Chan K, Tong AHY, Mohamad-Ramshan R, Berru M, Nakib D, Li G, Kardar GA, Carlyle JR, Moffat J, Durocher D, Di Noia JM, Bhagwat AS, Martin A., Free PMC Article

    03/5/2022
    The N-terminal domain of uracil-DNA glycosylase: Roles for disordered regions.

    The N-terminal domain of uracil-DNA glycosylase: Roles for disordered regions.
    Perkins JL, Zhao L., Free PMC Article

    08/14/2021
    Modulation of the Apurinic/Apyrimidinic Endonuclease Activity of Human APE1 and of Its Natural Polymorphic Variants by Base Excision Repair Proteins.

    Modulation of the Apurinic/Apyrimidinic Endonuclease Activity of Human APE1 and of Its Natural Polymorphic Variants by Base Excision Repair Proteins.
    Kladova OA, Alekseeva IV, Saparbaev M, Fedorova OS, Kuznetsov NA., Free PMC Article

    02/27/2021
    Macromolecular crowding induces compaction and DNA binding in the disordered N-terminal domain of hUNG2.

    Macromolecular crowding induces compaction and DNA binding in the disordered N-terminal domain of hUNG2.
    Rodriguez G, Orris B, Majumdar A, Bhat S, Stivers JT., Free PMC Article

    11/21/2020
    A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers.

    A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers.
    Baquero JM, Benítez-Buelga C, Fernández V, Urioste M, García-Giménez JL, Perona R, CIMBA Consortium, Benítez J, Osorio A., Free PMC Article

    04/25/2020
    We identified a distinct UNG1 isoform variant that is targeted to the cell nucleus where it supports antibody class switching and repairs genomic uracil. We propose that the nuclear UNG1 variant, which in contrast to UNG2 lacks a PCNA-binding motif, may be specialized to act on ssDNA through its ability to bind RPA

    Uracil-DNA glycosylase UNG1 isoform variant supports class switch recombination and repairs nuclear genomic uracil.
    Sarno A, Lundbæk M, Liabakk NB, Aas PA, Mjelle R, Hagen L, Sousa MML, Krokan HE, Kavli B., Free PMC Article

    11/30/2019
    Data indicate that patients with a combined profile of uracil DNA glycosylase (UDG)/breast cancer 1, early onset protein (BRCA1) had the poorest outcome.

    High UDG and BRCA1 expression is associated with adverse outcome in patients with pemetrexed treated non-small cell lung Cancer.
    Hashemi Sadraei N, Feng Y, Du L, Fu P, Haque S, Dowlati A, Gollamudi J, Pennell NA, Mekhail T, Avril S, Farver C, Gerson SL, Sharma N.

    10/5/2019
    Findings indicate that the of N-terminal domain (NTD) of human uracil DNA glycosylase (hUNG2) targets the enzyme to ssDNA-dsDNA junctions using replication protein A (RPA)-dependent and RPA-independent mechanisms.

    N-terminal domain of human uracil DNA glycosylase (hUNG2) promotes targeting to uracil sites adjacent to ssDNA-dsDNA junctions.
    Weiser BP, Rodriguez G, Cole PA, Stivers JT., Free PMC Article

    08/24/2019
    The study employs hybrid quantum mechanics calculations to investigate the exact Uracil DNA Glycosylase reaction mechanism of the nucleophile attack and the role of the conserved His148 residue. The calculations suggest that the C1'-N1 bond dissociation proceeds by a migration of the electrophilic sugar in the direction of the water nucleophile, resulting in a planar, oxocarbenium-like transition state.

    QM/MM Study of the Uracil DNA Glycosylase Reaction Mechanism: A Competition between Asp145 and His148.
    Naydenova E, Roßbach S, Ochsenfeld C.

    08/24/2019
    Study found associations between UNG rs246079 (A/G/T) and cervical squamous cell cancer (CSCC) or cervical intraepithelial neoplasia (CIN) III; observed no association between the UNG rs3219218 (A/G) polymorphism and risk of CIN III or CSCC.

    Genetic polymorphism (rs246079) of the DNA repair gene uracil N-glycosylase is associated with increased risk of cervical carcinoma in a Chinese population.
    Ye F, Wang H, Liu J, Cheng Q, Chen X, Chen H., Free PMC Article

    01/12/2019
    UDG depleted cancer cells displayed sustained DNA damage following 5-FdU treatment

    Inhibition of uracil DNA glycosylase sensitizes cancer cells to 5-fluorodeoxyuridine through replication fork collapse-induced DNA damage.
    Yan Y, Han X, Qing Y, Condie AG, Gorityala S, Yang S, Xu Y, Zhang Y, Gerson SL., Free PMC Article

    02/3/2018
    Uracil excision by bacterial UDG and human hUNG2 is reduced at uracils positioned directly 5' or 3' of a G-quadruplex DNA structures.

    G-quadruplex DNA structures can interfere with uracil glycosylase activity in vitro.
    Holton NW, Larson ED., Free PMC Article

    01/20/2018
    The UNG1-PRDX3 interaction protected UNG1 from reactive oxygen species-mediated degradation and prevented mitochondrial DNA oxidation.

    Hydrogen peroxide mediated mitochondrial UNG1-PRDX3 interaction and UNG1 degradation.
    Liu Z, Hu Y, Gong Y, Zhang W, Liu C, Wang Q, Deng H.

    12/30/2017
    Characterization of the ability of hUNG2 to translocate on DNA.

    Measurement of nanoscale DNA translocation by uracil DNA glycosylase in human cells.
    Esadze A, Rodriguez G, Weiser BP, Cole PA, Stivers JT., Free PMC Article

    12/30/2017
    Data indicate that DNA glycosylases MYH, UNG2, MPG, NTH1, NEIL1, 2 and 3 on nascent DNA.

    Monitoring of the spatial and temporal dynamics of BER/SSBR pathway proteins, including MYH, UNG2, MPG, NTH1 and NEIL1-3, during DNA replication.
    Bj Rås KØ, Sousa MML, Sharma A, Fonseca DM, S Gaard CK, Bj Rås M, Otterlei M., Free PMC Article

    10/28/2017
    Although the N-terminal domain has minimal effects on DNA binding and uracil excision kinetics, this study reports that this domain enhances the ability of human UNG2 to translocate on DNA chains as compared to the catalytic domain alone.

    Disordered N-Terminal Domain of Human Uracil DNA Glycosylase (hUNG2) Enhances DNA Translocation.
    Rodriguez G, Esadze A, Weiser BP, Schonhoft JD, Cole PA, Stivers JT., Free PMC Article

    10/14/2017
    Over-expression of uracil DNA glycosylase 2 in HepG2 protect cells against oxidative stress damage.

    [Over-expression of uracil DNA glycosylase 2 (UNG2) enhances the resistance to oxidative damage in HepG2 cells].
    Cao L, Cheng S, Du J, Guo Y, Huang X.

    09/16/2017
    Results suggest that the UNG2 N-terminus may serve as a flexible scaffold to tether PCNA and RPA at the replication fork, and that post-translational modifications on the UNG2 N-terminus disrupt formation of the PCNA-UNG2-RPA protein complex.

    Investigation of N-Terminal Phospho-Regulation of Uracil DNA Glycosylase Using Protein Semisynthesis.
    Weiser BP, Stivers JT, Cole PA., Free PMC Article

    08/26/2017
    HIV-1 vpr reprograms CRL4(DCAF1) E3 to direct HLTF for proteasome-dependent degradation independent from previously reported Vpr interactions with base excision repair enzyme uracil DNA glycosylase (UNG2) and crossover junction endonuclease MUS81, which Vpr also directs for degradation via CRL4(DCAF1) E3.

    HIV-1 and HIV-2 exhibit divergent interactions with HLTF and UNG2 DNA repair proteins.
    Hrecka K, Hao C, Shun MC, Kaur S, Swanson SK, Florens L, Washburn MP, Skowronski J., Free PMC Article

    08/12/2017
    Uracil DNA glycosylase (UNG) is the primary glycosylase responsible for the removal of uracils adjacent to cisplatin ICLs, whereas other uracil glycosylases can process uracils in the context of undamaged DNA.

    Differential role of base excision repair proteins in mediating cisplatin cytotoxicity.
    Sawant A, Floyd AM, Dangeti M, Lei W, Sobol RW, Patrick SM., Free PMC Article

    07/29/2017
    find that the energetic nature of the observed binding free energies of human 8-oxoguanine DNA glycosylase (hOGG1) and human uracil DNA glycosylase (hUNG) for undamaged DNA are derived from different sources. Although hOGG1 uses primarily nonelectrostatic binding interactions with nonspecific DNA, hUNG uses a salt-dependent electrostatic binding mode

    Comparative Effects of Ions, Molecular Crowding, and Bulk DNA on the Damage Search Mechanisms of hOGG1 and hUNG.
    Cravens SL, Stivers JT., Free PMC Article

    05/13/2017
    The authors show that Vpr can form a trimolecular complex with UNG2 and RPA32 and the positive effect of UNG2 and RPA32 on the reverse transcription process leading to optimal virus replication and dissemination between the primary target cells of HIV-1.

    Uracil DNA glycosylase interacts with the p32 subunit of the replication protein A complex to modulate HIV-1 reverse transcription for optimal virus dissemination.
    Herate C, Vigne C, Guenzel CA, Lambele M, Rouyez MC, Benichou S., Free PMC Article

    10/22/2016
    Data suggest novel mechanism in innate immunity allows cytokine TGF-beta to restrict viral circular DNA in hepatocyte nuclei via innate immunity; AID deaminates circular DNA of hepatitis B virus leading to DNA degradation; mechanism depends on UNG.

    TGF-β triggers HBV cccDNA degradation through AID-dependent deamination.
    Qiao Y, Han X, Guan G, Wu N, Sun J, Pak V, Liang G.

    06/28/2016
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