4fs2 › Citations

Basis of miscoding of the DNA adduct N2,3-ethenoguanine by human Y-family DNA polymerases.

Zhao L, Pence MG, Christov PP, Wawrzak Z, Choi JY, Rizzo CJ, Egli M, Guengerich FP
J Biol Chem 287 35516-35526 (2012)
Cited: 19 times
EuropePMC logo PMID: 22910910

Abstract

N(2),3-Ethenoguanine (N(2),3-εG) is one of the exocyclic DNA adducts produced by endogenous processes (e.g. lipid peroxidation) and exposure to bioactivated vinyl monomers such as vinyl chloride, which is a known human carcinogen. Existing studies exploring the miscoding potential of this lesion are quite indirect because of the lability of the glycosidic bond. We utilized a 2'-fluoro isostere approach to stabilize this lesion and synthesized oligonucleotides containing 2'-fluoro-N(2),3-ε-2'-deoxyarabinoguanosine to investigate the miscoding potential of N(2),3-εG by Y-family human DNA polymerases (pols). In primer extension assays, pol η and pol κ replicated through N(2),3-εG, whereas pol ι and REV1 yielded only 1-base incorporation. Steady-state kinetics revealed that dCTP incorporation is preferred opposite N(2),3-εG with relative efficiencies in the order of pol κ > REV1 > pol η ≈ pol ι, and dTTP misincorporation is the major miscoding event by all four Y-family human DNA pols. Pol ι had the highest dTTP misincorporation frequency (0.71) followed by pol η (0.63). REV1 misincorporated dTTP and dGTP with much lower frequencies. Crystal structures of pol ι with N(2),3-εG paired to dCTP and dTTP revealed Hoogsteen-like base pairing mechanisms. Two hydrogen bonds were observed in the N(2),3-εG:dCTP base pair, whereas only one appears to be present in the case of the N(2),3-εG:dTTP pair. Base pairing mechanisms derived from the crystal structures explain the slightly favored dCTP insertion for pol ι in steady-state kinetic analysis. Taken together, these results provide a basis for the mutagenic potential of N(2),3-εG.

Reviews - 4fs2 mentioned but not cited (1)

  1. Translesion Synthesis: Insights into the Selection and Switching of DNA Polymerases. Zhao L, Washington MT. Genes (Basel) 8 E24 (2017)

Articles - 4fs2 mentioned but not cited (1)

  1. Basis of miscoding of the DNA adduct N2,3-ethenoguanine by human Y-family DNA polymerases. Zhao L, Pence MG, Christov PP, Wawrzak Z, Choi JY, Rizzo CJ, Egli M, Guengerich FP. J Biol Chem 287 35516-35526 (2012)


Reviews citing this publication (5)

  1. Inflammation-induced DNA damage, mutations and cancer. Kay J, Thadhani E, Samson L, Engelward B. DNA Repair (Amst) 83 102673 (2019)
  2. Interplay between Cellular Metabolism and the DNA Damage Response in Cancer. Moretton A, Loizou JI. Cancers (Basel) 12 E2051 (2020)
  3. Mechanisms of mutagenesis: DNA replication in the presence of DNA damage. Liu B, Xue Q, Tang Y, Cao J, Guengerich FP, Zhang H. Mutat Res Rev Mutat Res 768 53-67 (2016)
  4. A rescue act: Translesion DNA synthesis past N(2) -deoxyguanosine adducts. Nair DT, Kottur J, Sharma R. IUBMB Life 67 564-574 (2015)
  5. Etheno adducts: from tRNA modifications to DNA adducts and back to miscoding ribonucleotides. Guengerich FP, Ghodke PP. Genes Environ 43 24 (2021)

Articles citing this publication (12)

  1. Intrinsic mutagenic properties of 5-chlorocytosine: A mechanistic connection between chronic inflammation and cancer. Fedeles BI, Freudenthal BD, Yau E, Singh V, Chang SC, Li D, Delaney JC, Wilson SH, Essigmann JM. Proc Natl Acad Sci U S A 112 E4571-80 (2015)
  2. Error-prone translesion synthesis past DNA-peptide cross-links conjugated to the major groove of DNA via C5 of thymidine. Wickramaratne S, Boldry EJ, Buehler C, Wang YC, Distefano MD, Tretyakova NY. J Biol Chem 290 775-787 (2015)
  3. Bypass of DNA-Protein Cross-links Conjugated to the 7-Deazaguanine Position of DNA by Translesion Synthesis Polymerases. Wickramaratne S, Ji S, Mukherjee S, Su Y, Pence MG, Lior-Hoffmann L, Fu I, Broyde S, Guengerich FP, Distefano M, Schärer OD, Sham YY, Tretyakova N. J Biol Chem 291 23589-23603 (2016)
  4. Next-generation sequencing reveals the biological significance of the N(2),3-ethenoguanine lesion in vivo. Chang SC, Fedeles BI, Wu J, Delaney JC, Li D, Zhao L, Christov PP, Yau E, Singh V, Jost M, Drennan CL, Marnett LJ, Rizzo CJ, Levine SS, Guengerich FP, Essigmann JM. Nucleic Acids Res 43 5489-5500 (2015)
  5. Replication past the butadiene diepoxide-derived DNA adduct S-[4-(N(6)-deoxyadenosinyl)-2,3-dihydroxybutyl]glutathione by DNA polymerases. Cho SH, Guengerich FP. Chem Res Toxicol 26 1005-1013 (2013)
  6. Non-bulky Lesions in Human DNA: the Ways of Formation, Repair, and Replication. Ignatov AV, Bondarenko KA, Makarova AV. Acta Naturae 9 12-26 (2017)
  7. Kinetic analysis of bypass of 7,8-dihydro-8-oxo-2'-deoxyguanosine by the catalytic core of yeast DNA polymerase η. Xue Q, Zhong M, Liu B, Tang Y, Wei Z, Guengerich FP, Zhang H. Biochimie 121 161-169 (2016)
  8. Mutagenic Bypass of an Oxidized Abasic Lesion-Induced DNA Interstrand Cross-Link Analogue by Human Translesion Synthesis DNA Polymerases. Xu W, Ouellette A, Ghosh S, O'Neill TC, Greenberg MM, Zhao L. Biochemistry 54 7409-7422 (2015)
  9. Tri-Cyclic Nucleobase Analogs and their Ribosides as Substrates of Purine-Nucleoside Phosphorylases. II Guanine and Isoguanine Derivatives. Stachelska-Wierzchowska A, Wierzchowski J, Górka M, Bzowska A, Wielgus-Kutrowska B. Molecules 24 E1493 (2019)
  10. Site-Specific Synthesis of Oligonucleotides Containing 6-Oxo-M1dG, the Genomic Metabolite of M1dG, and Liquid Chromatography-Tandem Mass Spectrometry Analysis of Its In Vitro Bypass by Human Polymerase ι. Christov PP, Richie-Jannetta R, Kingsley PJ, Vemulapalli A, Kim K, Sulikowski GA, Rizzo CJ, Ketkar A, Eoff RL, Rouzer CA, Marnett LJ. Chem Res Toxicol 34 2567-2578 (2021)
  11. A formamidopyrimidine derivative from the deoxyguanosine adduct produced by food contaminant acrylamide induces DNA replication block and mutagenesis. Akagi JI, Yokoi M, Miyake Y, Shirai T, Baba T, Cho YM, Hanaoka F, Sugasawa K, Iwai S, Ogawa K. J Biol Chem 299 105002 (2023)
  12. O6-2'-Deoxyguanosine-butylene-O6-2'-deoxyguanosine DNA Interstrand Cross-Links Are Replication-Blocking and Mutagenic DNA Lesions. Xu W, Kool D, O'Flaherty DK, Keating AM, Sacre L, Egli M, Noronha A, Wilds CJ, Zhao L. Chem Res Toxicol 29 1872-1882 (2016)


Quick links