Cellular effects of 5-formyluracil in DNA

Bjelland, Svein; Ånensen, Hilde; Knævelsrud, Ingeborg; Seeberg, Erling

doi:10.1016/s0921-8777(01)00085-4

Cited by 33 publications

(26 citation statements)

References 46 publications

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“…5-fodU and 5-hmdU are major products of oxidative damage of the methyl group of thymine [12, 19, 25]. Attack of hydroxyl radicals on the 5-methyl group generates 5-hydroperoxymethyluracil, the most stable thymine hydroperoxide [12].…”

Section: Resultsmentioning

confidence: 99%

“…Attack of hydroxyl radicals on the 5-methyl group generates 5-hydroperoxymethyluracil, the most stable thymine hydroperoxide [12]. It decomposes to the more stable products 5-fodU and 5-hmdU [12, 25]. Recent studies showed that 5-fodU is a potentially mutagenic lesion [25, 26].…”

Section: Resultsmentioning

confidence: 99%

“…It decomposes to the more stable products 5-fodU and 5-hmdU [12, 25]. Recent studies showed that 5-fodU is a potentially mutagenic lesion [25, 26]. It directs insertion of mismatched bases opposite the lesion during DNA synthesis in vitro [27].…”

Section: Resultsmentioning

confidence: 99%

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Error‐Prone Translesion DNA Synthesis byEscherichia coli DNA Polymerase IV (DinB) on Templates Containing 1,2‐dihydro‐2‐oxoadenine

Hori

Yonekura²,

Nohmi

et al. 2010

Journal of Nucleic Acids

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Escherichia coli DNA polymerase IV (Pol IV) is involved in bypass replication of damaged bases in DNA. Reactive oxygen species (ROS) are generated continuously during normal metabolism and as a result of exogenous stress such as ionizing radiation. ROS induce various kinds of base damage in DNA. It is important to examine whether Pol IV is able to bypass oxidatively damaged bases. In this study, recombinant Pol IV was incubated with oligonucleotides containing thymine glycol (dTg), 5-formyluracil (5-fodU), 5-hydroxymethyluracil (5-hmdU), 7,8-dihydro-8-oxoguanine (8-oxodG) and 1,2-dihydro-2-oxoadenine (2-oxodA). Primer extension assays revealed that Pol IV preferred to insert dATP opposite 5-fodU and 5-hmdU, while it inefficiently inserted nucleotides opposite dTg. Pol IV inserted dCTP and dATP opposite 8-oxodG, while the ability was low. It inserted dCTP more effectively than dTTP opposite 2-oxodA. Pol IV's ability to bypass these lesions decreased in the order: 2-oxodA > 5-fodU~5-hmdU > 8-oxodG > dTg. The fact that Pol IV preferred to insert dCTP opposite 2-oxodA suggests the mutagenic potential of 2-oxodA leading to A:T→G:C transitions. Hydrogen peroxide caused an ~2-fold increase in A:T→G:C mutations in E. coli, while the increase was significantly greater in E. coli overexpressing Pol IV. These results indicate that Pol IV may be involved in ROS-enhanced A:T→G:C mutations.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Error‐Prone Translesion DNA Synthesis byEscherichia coli DNA Polymerase IV (DinB) on Templates Containing 1,2‐dihydro‐2‐oxoadenine

Hori

Yonekura²,

Nohmi

et al. 2010

Journal of Nucleic Acids

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“…The presence of 5-foU in the DNA does not lead to replication block on both DNA strands; however high-fidelity DNA polymerases such as the Klenow fragment of DNA polymerase I, DNA polymerase alpha and gamma are able to incorporate any of the 4 dNTPs opposite 5-foU allowing transition and transversions [3]. The 5-foU residue is weakly mutagenic, with mutation frequencies in double-stranded vectors in the range of 0.01–0.04% [4].…”

Section: Introductionmentioning

confidence: 99%

Clustered DNA Lesions Containing 5-Formyluracil and AP Site: Repair via the BER System

et al. 2013

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Lesions in the DNA arise under ionizing irradiation conditions or various chemical oxidants as a single damage or as part of a multiply damaged site within 1–2 helical turns (clustered lesion). Here, we explored the repair opportunity of the apurinic/apyrimidinic site (AP site) composed of the clustered lesion with 5-formyluracil (5-foU) by the base excision repair (BER) proteins. We found, that if the AP site is shifted relative to the 5-foU of the opposite strand, it could be repaired primarily via the short-patch BER pathway. In this case, the cleavage efficiency of the AP site-containing DNA strand catalyzed by human apurinic/apyrimidinic endonuclease 1 (hAPE1) decreased under AP site excursion to the 3'-side relative to the lesion in the other DNA strand. DNA synthesis catalyzed by DNA polymerase lambda was more accurate in comparison to the one catalyzed by DNA polymerase beta. If the AP site was located exactly opposite 5-foU it was expected to switch the repair to the long-patch BER pathway. In this situation, human processivity factor hPCNA stimulates the process.

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“…Thymine glycol (Tg), 5-formyluracil (5-foU) and 5-hydroxymethyluracil (5-hmU) are the major oxidative products of thymine (Teebor et al, 1988;Bjelland et al, 2001;Zhang et al, 2000). These lesions are primarily repaired by endonu-clease III (Nth) and endonuclease VIII (Nei) in E. coli and by the homologues in S. cerevisiae, S. pombe, C. elegans and human cells (Zhang et al, 1995(Zhang et al, , 1997(Zhang et al, , 1999(Zhang et al, , 2000(Zhang et al, , 2003Bjelland et al, 1994Bjelland et al, , 1995Yonekura et al, 2007;Morinaga et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Structural and functional properties of CiNTH, an endonuclease III homologue of the ascidian <i>Ciona intestinalis</i>: critical role of N-terminal region

et al. 2012

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Oxidatively damaged bases in DNA can cause cell death, mutation and/or cancer induction. To overcome such deleterious effects of DNA base oxidation, cells are equipped with base excision repair (BER) initiated by DNA glycosylases. Endonuclease III (Nth), a major DNA glycosylase, mainly excises oxidatively damaged pyrimidines from DNA. The aims of this study were to obtain an overview of the repair mechanism of oxidatively damaged bases and to elucidate the function of BER in maintaining genome stability during embryogenesis and development. In this study, we used the ascidian Ciona intestinalis because at every developmental stage it is possible to observe the phenotype of individuals with DNA damage or mutations. Sequence alignment analysis revealed that the amino acid sequence of Ciona intestinalis Nth homologue (CiNTH) had high homology with those of Escherichia coli, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans and human Nth homologues. It was evident that two domains, the Helix-hairpin-Helix and 4Fe-4S cluster domains that are critical regions for the Nth activity, are well conserved in CiNTH. CiNTH efficiently complemented the sensitivity of E. coli nth nei mutant to H 2 O 2 . CiNTH was bifunctional, with DNA glycosylase and AP lyase activities. It removed thymine glycol, 5-formyluracil and 8-oxoguanine paired with G from DNA via a β-elimination reaction. Interestingly, the N-terminal 44 amino acids were essential for the DNA glycosylase activity of CiNTH.

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Cellular effects of 5-formyluracil in DNA

Cited by 33 publications

References 46 publications

Error‐Prone Translesion DNA Synthesis byEscherichia coli DNA Polymerase IV (DinB) on Templates Containing 1,2‐dihydro‐2‐oxoadenine

Error‐Prone Translesion DNA Synthesis byEscherichia coli DNA Polymerase IV (DinB) on Templates Containing 1,2‐dihydro‐2‐oxoadenine

Clustered DNA Lesions Containing 5-Formyluracil and AP Site: Repair via the BER System

Structural and functional properties of CiNTH, an endonuclease III homologue of the ascidian <i>Ciona intestinalis</i>: critical role of N-terminal region

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