Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids.

Research output: Contribution to journalConference article

179 Citations (Scopus)

Abstract

Genomes and their precursor nucleotides are highly exposed to reactive oxygen species, which are generated both as byproducts of oxygen respiration or molecular executors in the host defense, and by environmental exposure to ionizing radiation and chemicals. To counteract such oxidative damage in nucleic acids, mammalian cells are equipped with three distinct enzymes. MTH1 protein hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-2'-deoxyguanosine triphosphate and 2-hydroxy-2'-deoxyadenosine triphosphate (2-OH-dATP), to the corresponding monophosphates. We observed increased susceptibility to spontaneous carcinogenesis in MTH1-null mice, which exhibit an increased occurrence of A:T-->C:G and G:C-->T:A transversion mutations. 8-Oxoguanine (8-oxoG) DNA glycosylase, encoded by the OGG1 gene, and adenine DNA glycosylase, encoded by the MUTYH gene, are responsible for the suppression of G:C to T:A transversions caused by the accumulation of 8-oxoG in the genome. Deficiency of these enzymes leads to increased tumorigenesis in the lung and intestinal tract in mice, respectively. MUTYH deficiency may also increase G:C to T:A transversions through the misincorporation of 2-OH-dATP, especially in the intestinal tract, since MUTYH can excise 2-hydroxyadenine opposite guanine in genomic DNA and the repair activity is selectively impaired by a mutation found in patients with autosomal recessive colorectal adenomatous polyposis.

Original languageEnglish
Pages (from-to)373-379
Number of pages7
JournalBiological chemistry
Volume387
Issue number4
DOIs
Publication statusPublished - Jan 1 2006

Fingerprint

DNA Glycosylases
Mutagenesis
Nucleic Acids
Carcinogenesis
Genes
Genome
Purine Nucleosides
Oxidation
Mutation
Environmental Exposure
Guanine
Enzymes
Ionizing Radiation
DNA Repair
Reactive Oxygen Species
Respiration
Nucleotides
Oxygen
Lung
Ionizing radiation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids. / Nakabeppu, Yusaku; Kunihiko, Sakumi; Sakamoto, Katsumi; Tsuchimoto, Daisuke; Tsuzuki, Teruhisa; Nakatsu, Yoshimichi.

In: Biological chemistry, Vol. 387, No. 4, 01.01.2006, p. 373-379.

Research output: Contribution to journalConference article

@article{5e0a9940807c4a12ba49ac8b42bf4b76,
title = "Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids.",
abstract = "Genomes and their precursor nucleotides are highly exposed to reactive oxygen species, which are generated both as byproducts of oxygen respiration or molecular executors in the host defense, and by environmental exposure to ionizing radiation and chemicals. To counteract such oxidative damage in nucleic acids, mammalian cells are equipped with three distinct enzymes. MTH1 protein hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-2'-deoxyguanosine triphosphate and 2-hydroxy-2'-deoxyadenosine triphosphate (2-OH-dATP), to the corresponding monophosphates. We observed increased susceptibility to spontaneous carcinogenesis in MTH1-null mice, which exhibit an increased occurrence of A:T-->C:G and G:C-->T:A transversion mutations. 8-Oxoguanine (8-oxoG) DNA glycosylase, encoded by the OGG1 gene, and adenine DNA glycosylase, encoded by the MUTYH gene, are responsible for the suppression of G:C to T:A transversions caused by the accumulation of 8-oxoG in the genome. Deficiency of these enzymes leads to increased tumorigenesis in the lung and intestinal tract in mice, respectively. MUTYH deficiency may also increase G:C to T:A transversions through the misincorporation of 2-OH-dATP, especially in the intestinal tract, since MUTYH can excise 2-hydroxyadenine opposite guanine in genomic DNA and the repair activity is selectively impaired by a mutation found in patients with autosomal recessive colorectal adenomatous polyposis.",
author = "Yusaku Nakabeppu and Sakumi Kunihiko and Katsumi Sakamoto and Daisuke Tsuchimoto and Teruhisa Tsuzuki and Yoshimichi Nakatsu",
year = "2006",
month = "1",
day = "1",
doi = "10.1515/BC.2006.050",
language = "English",
volume = "387",
pages = "373--379",
journal = "Biological Chemistry",
issn = "1431-6730",
publisher = "Walter de Gruyter GmbH & Co. KG",
number = "4",

}

TY - JOUR

T1 - Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids.

AU - Nakabeppu, Yusaku

AU - Kunihiko, Sakumi

AU - Sakamoto, Katsumi

AU - Tsuchimoto, Daisuke

AU - Tsuzuki, Teruhisa

AU - Nakatsu, Yoshimichi

PY - 2006/1/1

Y1 - 2006/1/1

N2 - Genomes and their precursor nucleotides are highly exposed to reactive oxygen species, which are generated both as byproducts of oxygen respiration or molecular executors in the host defense, and by environmental exposure to ionizing radiation and chemicals. To counteract such oxidative damage in nucleic acids, mammalian cells are equipped with three distinct enzymes. MTH1 protein hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-2'-deoxyguanosine triphosphate and 2-hydroxy-2'-deoxyadenosine triphosphate (2-OH-dATP), to the corresponding monophosphates. We observed increased susceptibility to spontaneous carcinogenesis in MTH1-null mice, which exhibit an increased occurrence of A:T-->C:G and G:C-->T:A transversion mutations. 8-Oxoguanine (8-oxoG) DNA glycosylase, encoded by the OGG1 gene, and adenine DNA glycosylase, encoded by the MUTYH gene, are responsible for the suppression of G:C to T:A transversions caused by the accumulation of 8-oxoG in the genome. Deficiency of these enzymes leads to increased tumorigenesis in the lung and intestinal tract in mice, respectively. MUTYH deficiency may also increase G:C to T:A transversions through the misincorporation of 2-OH-dATP, especially in the intestinal tract, since MUTYH can excise 2-hydroxyadenine opposite guanine in genomic DNA and the repair activity is selectively impaired by a mutation found in patients with autosomal recessive colorectal adenomatous polyposis.

AB - Genomes and their precursor nucleotides are highly exposed to reactive oxygen species, which are generated both as byproducts of oxygen respiration or molecular executors in the host defense, and by environmental exposure to ionizing radiation and chemicals. To counteract such oxidative damage in nucleic acids, mammalian cells are equipped with three distinct enzymes. MTH1 protein hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-2'-deoxyguanosine triphosphate and 2-hydroxy-2'-deoxyadenosine triphosphate (2-OH-dATP), to the corresponding monophosphates. We observed increased susceptibility to spontaneous carcinogenesis in MTH1-null mice, which exhibit an increased occurrence of A:T-->C:G and G:C-->T:A transversion mutations. 8-Oxoguanine (8-oxoG) DNA glycosylase, encoded by the OGG1 gene, and adenine DNA glycosylase, encoded by the MUTYH gene, are responsible for the suppression of G:C to T:A transversions caused by the accumulation of 8-oxoG in the genome. Deficiency of these enzymes leads to increased tumorigenesis in the lung and intestinal tract in mice, respectively. MUTYH deficiency may also increase G:C to T:A transversions through the misincorporation of 2-OH-dATP, especially in the intestinal tract, since MUTYH can excise 2-hydroxyadenine opposite guanine in genomic DNA and the repair activity is selectively impaired by a mutation found in patients with autosomal recessive colorectal adenomatous polyposis.

UR - http://www.scopus.com/inward/record.url?scp=33745485302&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745485302&partnerID=8YFLogxK

U2 - 10.1515/BC.2006.050

DO - 10.1515/BC.2006.050

M3 - Conference article

C2 - 16606334

AN - SCOPUS:33745485302

VL - 387

SP - 373

EP - 379

JO - Biological Chemistry

JF - Biological Chemistry

SN - 1431-6730

IS - 4

ER -