Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids.

2.50
Hdl Handle:
http://hdl.handle.net/10146/57774
Title:
Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids.
Authors:
Nakabeppu, Yusaku; Sakumi, Kunihiko; Sakamoto, Katsumi; Tsuchimoto, Daisuke; Tsuzuki, Teruhisa; Nakatsu, Yoshimichi
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.
Citation:
Biol. Chem. 2006, 387 (4):373-379
Journal:
Biological chemistry
Issue Date:
Apr-2006
URI:
http://hdl.handle.net/10146/57774
DOI:
10.1515/BC.2006.050
PubMed ID:
16606334
Additional Links:
http://www.reference-global.com/doi/abs/10.1515/BC.2006.050
Type:
Article
Language:
en
Description:
KEYWORDS CLASSIFICATION: adverse effects;Animals;chemistry;deficiency;DNA Damage;DNA Glycosylases;DNA Repair;DNA Repair Enzymes;Enzymes;genetics;Genomics;Guanine;Hydrolases;Intestinal Neoplasms;Japan;Liver Neoplasms;metabolism;mechanisms of carcinogenesis;Mice;Mutagenesis;Mutation;Neoplasms;Nucleic Acids;Oxidation-Reduction;Oxidative Stress;Phosphoric Monoester Hydrolases;Skin Neoplasms;Ultraviolet Rays.
ISSN:
1431-6730
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorNakabeppu, Yusaku-
dc.contributor.authorSakumi, Kunihiko-
dc.contributor.authorSakamoto, Katsumi-
dc.contributor.authorTsuchimoto, Daisuke-
dc.contributor.authorTsuzuki, Teruhisa-
dc.contributor.authorNakatsu, Yoshimichi-
dc.date.accessioned2009-03-30T08:03:38Z-
dc.date.available2009-03-30T08:03:38Z-
dc.date.issued2006-04-
dc.identifier.citationBiol. Chem. 2006, 387 (4):373-379en
dc.identifier.issn1431-6730-
dc.identifier.pmid16606334-
dc.identifier.doi10.1515/BC.2006.050-
dc.identifier.urihttp://hdl.handle.net/10146/57774-
dc.descriptionKEYWORDS CLASSIFICATION: adverse effects;Animals;chemistry;deficiency;DNA Damage;DNA Glycosylases;DNA Repair;DNA Repair Enzymes;Enzymes;genetics;Genomics;Guanine;Hydrolases;Intestinal Neoplasms;Japan;Liver Neoplasms;metabolism;mechanisms of carcinogenesis;Mice;Mutagenesis;Mutation;Neoplasms;Nucleic Acids;Oxidation-Reduction;Oxidative Stress;Phosphoric Monoester Hydrolases;Skin Neoplasms;Ultraviolet Rays.en
dc.description.abstractGenomes 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.en
dc.language.isoenen
dc.relation.urlhttp://www.reference-global.com/doi/abs/10.1515/BC.2006.050en
dc.subject2-hydroxyadenineen
dc.subject8-oxoguanineen
dc.subjectMTH1en
dc.subjectMUTYHen
dc.subjectOGG1en
dc.subjectOxidative damageen
dc.subject.meshAnimals-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Glycosylases-
dc.subject.meshDNA Repair Enzymes-
dc.subject.meshGuanine-
dc.subject.meshIntestinal Neoplasms-
dc.subject.meshLiver Neoplasms-
dc.subject.meshMice-
dc.subject.meshMutagenesis-
dc.subject.meshMutation-
dc.subject.meshNeoplasms-
dc.subject.meshNucleic Acids-
dc.subject.meshOxidation-Reduction-
dc.subject.meshOxidative Stress-
dc.subject.meshPhosphoric Monoester Hydrolases-
dc.subject.meshSkin Neoplasms-
dc.subject.meshUltraviolet Rays-
dc.titleMutagenesis and carcinogenesis caused by the oxidation of nucleic acids.en
dc.typeArticleen
dc.identifier.journalBiological chemistryen

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