Guanosine in a Single Stranded Region of Anticodon Stem–Loop tRNA Models is Prone to Oxidatively Generated Damage Resulting in Dehydroguanidinohydantoin and Spiroiminodihydantoin Lesions

Tomaszewska-Antczak, Agnieszka; Guga, Piotr; Nawrot, Barbara; Pratviel, Geneviève

doi:10.1002/chem.201406409

Cited by 8 publications

(11 citation statements)

References 33 publications

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“…In contrast, the use of cyt c /H 2 O 2 resulted in a significant decrease in the S2U content and an increased amount of H2U. For the reactions performed for 1 and 3 h, the ratio of the canonical nucleosides remained virtually constant, which confirmed that the guanine residues in an RNA chain were not oxidized under the conditions applied …”

Section: Resultsmentioning

confidence: 80%

Cytochrome cCatalyzes the Hydrogen Peroxide‐Assisted Oxidative Desulfuration of 2‐Thiouridines in Transfer RNAs

et al. 2018

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The 5-substituted 2-thiouridines (R5S2Us) present in the first (wobble) position of the anticodon of transfer RNAs (tRNAs) contribute to accuracy in reading mRNA codons and tuning protein synthesis. Previously, we showed that, under oxidative stress conditions in vitro, R5S2Us were sensitive to hydrogen peroxide (H O ) and that their oxidative desulfuration produced 5-substituted uridines (R5Us) and 4-pyrimidinone nucleosides (R5H2Us) at a ratio that depended on the pH and an R5 substituent. Here, we demonstrate that the desulfuration of 2-thiouridines, either alone or within an RNA/tRNA chain, is catalyzed by cytochrome c (cyt c). Its kinetics are similar to those of Fenton-type catalytic 2-thiouridine (S2U) desulfuration. Cyt c/H O - and Fe -mediated reactions deliver predominantly 4-pyrimidinone nucleoside (H2U)-type products. The pathway of the cyt c/H O -peroxidase-mediated S2U→H2U transformation through uridine sulfenic (U-SOH), sulfinic (U-SO H), and sulfonic (U-SO H) intermediates is confirmed by LC-MS. The cyt c/H O -mediated oxidative damage of S2U-tRNA may have biological relevance through alteration of the cellular functions of transfer RNA.

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Section: Resultsmentioning

confidence: 80%

Cytochrome cCatalyzes the Hydrogen Peroxide‐Assisted Oxidative Desulfuration of 2‐Thiouridines in Transfer RNAs

et al. 2018

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“…Studies to monitor cellular excretion of OG from DNA or RNA observe up to ~3-fold more OG in RNA than DNA supporting high levels of RNA oxidation in vivo [138]. Reports from our laboratory [139, 140], Pratviel and coworkers [141], and Thorp and coworkers [142] have described RNA oxidation in various contexts. The recent work by Pratviel and coworkers analyzed G oxidation by a manganese porphyrin complex and KHSO 5 in model anticodon tRNA stem-loops to identify the oxidation product Sp [141].…”

Section: Additional Contexts and Reaction Partners Of G Studied Unmentioning

confidence: 95%

“…Reports from our laboratory [139, 140], Pratviel and coworkers [141], and Thorp and coworkers [142] have described RNA oxidation in various contexts. The recent work by Pratviel and coworkers analyzed G oxidation by a manganese porphyrin complex and KHSO 5 in model anticodon tRNA stem-loops to identify the oxidation product Sp [141]. We found 1 O 2 oxidation of G in ssRNA can yield Sp or Gh in a pH-dependent reaction [140], and a nickel macrocycle to activate the oxidant KHSO 5 yields 2Ih [140].…”

Section: Additional Contexts and Reaction Partners Of G Studied Unmentioning

confidence: 99%

Formation and processing of DNA damage substrates for the hNEIL enzymes

Fleming

Burrows

2017

Free Radical Biology and Medicine

112

135

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Reactive oxygen species (ROS) are harnessed by the cell for signaling at the same time as being detrimental to cellular components such as DNA. The genome and transcriptome contain instructions that can alter cellular processes when oxidized. The guanine (G) heterocycle in the nucleotide pool, DNA, or RNA is the base most prone to oxidation. The oxidatively-derived products of G consistently observed in high yields from hydroxyl radical, carbonate radical, or singlet oxygen oxidations under conditions modeling the cellular reducing environment are discussed. The major G base oxidation products are 8-oxo-7,8-dihydroguanine (OG), 5-carboxamido-5-formamido-2-iminohydantoin (2Ih), spiroiminodihydantoin (Sp), and 5-guanidinohydantoin (Gh). The yields of these products show dependency on the oxidant and the reaction context that includes nucleoside, single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), and G-quadruplex DNA (G4-DNA) structures. Upon formation of these products in cells, they are recognized by the DNA glycosylases in the base excision repair (BER) pathway. This review focuses on initiation of BER by the mammalian Nei-like1-3 (NEIL1-3) glycosylases for removal of 2Ih, Sp, and Gh. The unique ability of the human NEILs to initiate removal of the hydantoins in ssDNA, bulge-DNA, bubble-DNA, dsDNA, and G4-DNA is outlined. Additionally, when Gh exists in a G4 DNA found in a gene promoter, NEIL-mediated repair is modulated by the plasticity of the G4-DNA structure provided by additional G-runs flanking the sequence. On the basis of these observations and cellular studies from the literature, the interplay between DNA oxidation and BER to alter gene expression is discussed.

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“…37, 38 OG has been found in both cellular DNA and RNA, while Gh and Sp have thus far been characterized only in cellular DNA and in RNA oligomers mimicking the tRNA anticodon loop or short single strands of RNA. 18, 39, 40 The latter lesion, Sp, exists as a pair of enantiomers ( R -Sp and S -Sp) as the free base, which form a pair of diastereomers once attached to the chiral ribose or 2′-deoxyribose components in nucleic acids. 41 …”

Section: Introductionmentioning

confidence: 99%

Reverse Transcription Past Products of Guanine Oxidation in RNA Leads to Insertion of A and C opposite 8-Oxo-7,8-dihydroguanine and A and G opposite 5-Guanidinohydantoin and Spiroiminodihydantoin Diastereomers

2017

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Reactive oxygen species, both endogenous and exogenous, can damage nucleobases of RNA and DNA. Among the nucleobases, guanine has the lowest redox potential making it a major target of oxidation. Although, RNA is more prone to oxidation than DNA, oxidation of guanine in RNA has been studied to a significantly lesser extent. One of the reasons for this is that many tools that were previously developed to study oxidation of DNA cannot be used on RNA. In the current study, the lack of a method for seeking sites of modification in RNA where oxidation occurs is addressed. For this purpose, reverse transcription of RNA containing major products of guanine oxidation was used. Extension of a DNA primer annealed to an RNA template containing 8-oxo-7,8-dihydroguanine (OG), 5-guanidinohydantoin (Gh), or the R and S diastereomers of spiroiminodihydantoin (Sp) was studied under standing start conditions. SuperScript III reverse transcriptase is capable of bypassing these lesions in RNA inserting predominantly A opposite OG, predominantly G opposite Gh, and almost an equal mixture of A and G opposite the Sp diastereomers. These data should allow RNA sequencing of guanine oxidation products by following characteristic mutation signatures formed by the reverse transcriptase during primer elongation past G oxidation sites in the template RNA strand.

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Guanosine in a Single Stranded Region of Anticodon Stem–Loop tRNA Models is Prone to Oxidatively Generated Damage Resulting in Dehydroguanidinohydantoin and Spiroiminodihydantoin Lesions

Cited by 8 publications

References 33 publications

Cytochrome cCatalyzes the Hydrogen Peroxide‐Assisted Oxidative Desulfuration of 2‐Thiouridines in Transfer RNAs

Cytochrome cCatalyzes the Hydrogen Peroxide‐Assisted Oxidative Desulfuration of 2‐Thiouridines in Transfer RNAs

Formation and processing of DNA damage substrates for the hNEIL enzymes

Reverse Transcription Past Products of Guanine Oxidation in RNA Leads to Insertion of A and C opposite 8-Oxo-7,8-dihydroguanine and A and G opposite 5-Guanidinohydantoin and Spiroiminodihydantoin Diastereomers

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