Unlike Catalyzing Error-Free Bypass of 8-OxodGuo, DNA Polymerase λ Is Responsible for a Significant Part of Fapy·dG-Induced G → T Mutations in Human Cells

Pande, Paritosh; Haraguchi, Kazuhiro; Jiang, Yulin; Greenberg, Marc M.; Basu, Ashis K.

doi:10.1021/acs.biochem.5b00119

Cited by 34 publications

(62 citation statements)

References 28 publications

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“…Moreover, G➔A and G➔C mutations were detected. Recently, Pande et al examined the mutagenic properties of G O in the 5’-TG O N-3’ (N = A, G, C, and T) sequence in human 293T cells [37]. The frequencies of G➔T targeted mutations were 5–11 %, and G➔A and 2-base deletion mutations were also induced.…”

Section: Introductionmentioning

confidence: 99%

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Mutations induced by 8-hydroxyguanine (8-oxo-7,8-dihydroguanine), a representative oxidized base, in mammalian cells

Suzuki

Kamiya

2016

Genes and Environ

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Guanine oxidation occurs in both DNA and the cellular nucleotide pool, and one of the major products is 8-hydroxyguanine (8-oxo-7,8-dihydroguanine). The mutagenic potentials of this oxidized base have been examined in various experimental systems. In this review, we summarize the mutagenicity of the base in mammalian cells. We also describe the effects of specialized DNA polymerases, DNA repair proteins, and nucleotide pool sanitization enzymes.

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Section: Introductionmentioning

confidence: 99%

“…Interestingly, the knockdown of DNA pol λ increased the 2-base deletion mutations induced by G O in single-stranded DNA [37]. This result suggested that DNA pol λ is involved in the error-free bypass of G O , by preventing the 2-base deletion.…”

Section: Introductionmentioning

confidence: 99%

Mutations induced by 8-hydroxyguanine (8-oxo-7,8-dihydroguanine), a representative oxidized base, in mammalian cells

Suzuki

Kamiya

2016

Genes and Environ

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“…The mutagenic potential of the Fapy‐dG adduct has been previously investigated in both mammalian [Kalam et al, ; Pande et al, ] and bacterial systems [Patro et al, ]. These studies revealed a dominance of G → T transversions, similar to mutagenic signature of the 8‐oxo‐dG adduct [Shibutani et al, ; Kalam et al, ; Yuan et al, ; Pande et al, ]. Despite this similarity, the conformation of the nucleotide adducts in a replication complex during error‐prone bypass could be different.…”

Section: Introductionmentioning

confidence: 99%

Error‐prone replication bypass of the imidazole ring‐opened formamidopyrimidine deoxyguanosine adduct

Sha

Minko

Malik

et al. 2017

Environ and Mol Mutagen

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Addition of hydroxyl radicals to the C8 position of 2′-deoxyguanosine generates an 8-hydroxyguanyl radical that can be converted into either 8-oxo-7,8-dihydro-2′-deoxyguanosine or N-(2-deoxy-D-pentofuranosyl)-N-(2,6-diamino-4-hydroxy-5-formamidopyrimidine) (Fapy-dG). The Fapy-dG adduct can adopt different conformations and in particular, can exist in unnatural α anomeric configuration in addition to canonical β configuration. Previous studies reported that in 5′-TGN-3′ sequences, Fapy-dG predominantly induced G → T transversions in both mammalian cells and Escherichia coli, suggesting that mutations could be formed either via insertion of a dA opposite the 5′ dT due to primer/template misalignment or as result of direct miscoding. To address this question, single-stranded vectors containing a site-specific Fapy-dG adduct were generated to vary the identity of the 5′ nucleotide. Following vector replication in primate cells (COS7), complex mutation spectra were observed that included ~3–5% G → T transversions and ~14–21% G → A transitions. There was no correlation apparent between the identity of the 5′ nucleotide and spectra of mutations. When conditions for vector preparation were modified to favor the β anomer, frequencies of both G → T and G → A substitutions were significantly reduced. Mutation frequencies in wild type E. coli and a mutant deficient in damage-inducible DNA polymerases, were significantly lower than detected in COS7 and spectra were dominated by deletions. Thus, mutagenic bypass of Fapy-dG can proceed via mechanisms that are different from the previously proposed primer/template misalignment or direct misinsertions of dA or dT opposite the β anomer of Fapy-dG.

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“…32, 33 N 5 -Substituted Fapy-dG adducts derived from aflatoxin B 1 epoxide (AFB 1 -Fapy-dG) and methylating agents (MeFapy-dG) have been reported to be persistent lesions in rodents. 34, 35 The AFB 1 -Fapy-dG and MeFapy-dG adducts have also been shown to be mutagenic in COS-7 cells.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Nitrogen Mustard Formamidopyrimidine Adduct Formation of Bis(2-chloroethyl)ethylamine with Calf Thymus DNA and a Human Mammary Cancer Cell Line

Gruppi

Hejazi

Christov

et al. 2015

Chem. Res. Toxicol.

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A robust, quantitative ultraperformance liquid chromatography ion trap multistage scanning mass spectrometric (UPLC/MS3) method was established to characterize and measure five deoxyguanosine (dG) adducts formed by reaction of the chemotherapeutic nitrogen mustard (NM) bis-(2-chloroethyl)ethylamine with calf thymus (CT) DNA. In addition to the known N7-guanine (NM-G) adduct and its crosslink (G-NM-G), the ring-opened formamidopyrimidine (FapyG) mono-adduct (NM-FapyG) and cross-links in which one (FapyG-NM-G) or both (FapyG-NM-FapyG) guanines underwent ring-opening to FapyG units were identified. Authentic standards of all adducts were synthesized and characterized by NMR and mass spectrometry. These adducts were quantified in CT DNA treated with NM (1 μM) as their deglycosylated bases. A two-stage neutral thermal hydrolysis was developed to mitigate the artifactual formation of ring-opened FapyG adducts involving hydrolysis of the cationic adduct at 37 °C, followed by hydrolysis of the FapyG adducts at 95 °C. The limit of quantification values ranged between 0.3 and 1.6 adducts per 107 DNA bases, when the equivalent of 5 μg DNA hydrolysate was assayed on column. The principal adduct formed was the G-NM-G cross-link, followed by the NM-G mono-adduct; the FapyG-NM-FapyG adduct was at the limit of detection. The NM-FapyG adducts formed in CT DNA at a level of ~20% that of the NM-G adduct. NM-FapyG has not been previously quanitified and the FapyG-NM-G and FapyG-NM-FapyG adducts have not be previously characterized. Our validated analytical method was then applied to measure DNA adduct formation in the MDA-MB-231 mammary tumor cell line exposed to NM (100 μM) for 24 h. The major adduct formed was NM-G (970 adducts per 107 bases), followed by G-NM-G (240 adducts per 107 bases) and NM-FapyG (180 adducts per 107 bases), and lastly the FapyG-NM-G cross-link adduct (6.0 adducts per 107 bases). These lesions are expected to contribute to the NM-mediated toxicity and genotoxicity in vivo.

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Unlike Catalyzing Error-Free Bypass of 8-OxodGuo, DNA Polymerase λ Is Responsible for a Significant Part of Fapy·dG-Induced G → T Mutations in Human Cells

Cited by 34 publications

References 28 publications

Mutations induced by 8-hydroxyguanine (8-oxo-7,8-dihydroguanine), a representative oxidized base, in mammalian cells

Mutations induced by 8-hydroxyguanine (8-oxo-7,8-dihydroguanine), a representative oxidized base, in mammalian cells

Error‐prone replication bypass of the imidazole ring‐opened formamidopyrimidine deoxyguanosine adduct

Characterization of Nitrogen Mustard Formamidopyrimidine Adduct Formation of Bis(2-chloroethyl)ethylamine with Calf Thymus DNA and a Human Mammary Cancer Cell Line

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