Translesion Synthesis Across 1,N2-Ethenoguanine by Human DNA Polymerases
Identifieur interne : 002D61 ( Main/Exploration ); précédent : 002D60; suivant : 002D62Translesion Synthesis Across 1,N2-Ethenoguanine by Human DNA Polymerases
Auteurs : Jeong-Yun Choi [Corée du Sud] ; Hong Zang [Corée du Sud] ; Karen C. Angel [Corée du Sud] ; Ivan D. Kozekov [Corée du Sud] ; Angela K. Goodenough [Corée du Sud, États-Unis] ; Carmelo J. Rizzo [Corée du Sud] ; F. Peter Guengerich [Corée du Sud, États-Unis]Source :
- Chemical Research in Toxicology [ 0893-228x ] ; 2006.
Abstract
1,N2-Etheno(ε)guanine (ε) is formed in DNA as a result of exposure to certain vinyl monomers (e.g., vinyl chloride) or from lipid peroxidation. This lesion has been shown to be mutagenic in bacteria and mammalian cells. 1,N2-ε-G has been shown to block several model replicative DNA polymerases (pols), with limited bypass. Recently, an archebacterial DNA pol, Sulfolobus solfataricus Dpo4, has been shown to copy past 1,N2-ε-G. In this study, we examined the abilities of recombinant, full-length human pol δ and three human translesion DNA pols to copy past 1,N2-ε-G. The replicative pol, pol δ, was completely blocked. Pols ι and κ showed similar rates of incorporation of dTTP and dCTP. Pol η was clearly the most active of these pols in copying past 1,N2-ε-G, incorporating in the order dGTP > dATP > dCTP, regardless of whether the base 5‘ of 1,N2-ε-G in the template was C or T. Pol η also had the highest error frequency opposite 1,N2-ε-G. Analysis of the extended products of the pol η reactions by mass spectrometry indicated only two products, both of which had G incorporated opposite 1,N2-ε-G and all other base pairing being normal (i.e., G:C and A:T). One-half of the products contained an additional A at the 3‘-end, presumably arising from a noninformational blunt end addition or possibly a slipped insertion mechanism at the end of the primer−template replication process. In summary, the most efficient of the four human DNA pols was pol η, which appeared to insert G opposite 1,N2-ε-G and then copy correctly. This pattern differs with the same oligonucleotide sequences and 1,N2-ε-G observed using Dpo4, emphasizing the importance of pols in mutagenesis events.
Url:
DOI: 10.1021/tx060051v
Affiliations:
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Angel</name><affiliation wicri:level="3"><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Departments of Biochemistry and Chemistry and Center in Molecular Toxicology, Vanderbilt University,Nashville, Tennessee 37232-0146, and Department of Pharmacology, Ewha Womans University,Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation></affiliation></author><author><name sortKey="Kozekov, Ivan D" sort="Kozekov, Ivan D" uniqKey="Kozekov I" first="Ivan D." last="Kozekov">Ivan D. Kozekov</name><affiliation wicri:level="3"><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Departments of Biochemistry and Chemistry and Center in Molecular Toxicology, Vanderbilt University,Nashville, Tennessee 37232-0146, and Department of Pharmacology, Ewha Womans University,Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation></affiliation></author><author><name sortKey="Goodenough, Angela K" sort="Goodenough, Angela K" uniqKey="Goodenough A" first="Angela K." last="Goodenough">Angela K. Goodenough</name><affiliation wicri:level="3"><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Departments of Biochemistry and Chemistry and Center in Molecular Toxicology, Vanderbilt University,Nashville, Tennessee 37232-0146, and Department of Pharmacology, Ewha Womans University,Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea> Formerly Angela K. Brock. Present address: Wadsworth ResearchCenter, Albany</wicri:cityArea></affiliation></author><author><name sortKey="Rizzo, Carmelo J" sort="Rizzo, Carmelo J" uniqKey="Rizzo C" first="Carmelo J." last="Rizzo">Carmelo J. Rizzo</name><affiliation wicri:level="3"><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Departments of Biochemistry and Chemistry and Center in Molecular Toxicology, Vanderbilt University,Nashville, Tennessee 37232-0146, and Department of Pharmacology, Ewha Womans University,Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation></affiliation></author><author><name sortKey="Guengerich, F Peter" sort="Guengerich, F Peter" uniqKey="Guengerich F" first="F. Peter" last="Guengerich">F. Peter Guengerich</name><affiliation wicri:level="3"><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Departments of Biochemistry and Chemistry and Center in Molecular Toxicology, Vanderbilt University,Nashville, Tennessee 37232-0146, and Department of Pharmacology, Ewha Womans University,Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Chemical Research in Toxicology</title><title level="j" type="abbrev">Chem. Res. Toxicol.</title><idno type="ISSN">0893-228x</idno><idno type="eISSN">1520-5010</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published">2006</date><date type="published">2006</date><biblScope unit="vol">19</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="879">879</biblScope><biblScope unit="page" to="886">886</biblScope></imprint><idno type="ISSN">0893-228x</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0893-228x</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">1,N2-Etheno(ε)guanine (ε) is formed in DNA as a result of exposure to certain vinyl monomers (e.g., vinyl chloride) or from lipid peroxidation. This lesion has been shown to be mutagenic in bacteria and mammalian cells. 1,N2-ε-G has been shown to block several model replicative DNA polymerases (pols), with limited bypass. Recently, an archebacterial DNA pol, Sulfolobus solfataricus Dpo4, has been shown to copy past 1,N2-ε-G. In this study, we examined the abilities of recombinant, full-length human pol δ and three human translesion DNA pols to copy past 1,N2-ε-G. The replicative pol, pol δ, was completely blocked. Pols ι and κ showed similar rates of incorporation of dTTP and dCTP. Pol η was clearly the most active of these pols in copying past 1,N2-ε-G, incorporating in the order dGTP > dATP > dCTP, regardless of whether the base 5‘ of 1,N2-ε-G in the template was C or T. Pol η also had the highest error frequency opposite 1,N2-ε-G. Analysis of the extended products of the pol η reactions by mass spectrometry indicated only two products, both of which had G incorporated opposite 1,N2-ε-G and all other base pairing being normal (i.e., G:C and A:T). One-half of the products contained an additional A at the 3‘-end, presumably arising from a noninformational blunt end addition or possibly a slipped insertion mechanism at the end of the primer−template replication process. In summary, the most efficient of the four human DNA pols was pol η, which appeared to insert G opposite 1,N2-ε-G and then copy correctly. This pattern differs with the same oligonucleotide sequences and 1,N2-ε-G observed using Dpo4, emphasizing the importance of pols in mutagenesis events.</div></front></TEI><affiliations><list><country><li>Corée du Sud</li><li>États-Unis</li></country><region><li>Région capitale de Séoul</li><li>État de New York</li></region><settlement><li>Séoul</li></settlement></list><tree><country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Choi, Jeong Yun" sort="Choi, Jeong Yun" uniqKey="Choi J" first="Jeong-Yun" last="Choi">Jeong-Yun Choi</name></region><name sortKey="Angel, Karen C" sort="Angel, Karen C" uniqKey="Angel K" first="Karen C." last="Angel">Karen C. Angel</name><name sortKey="Goodenough, Angela K" sort="Goodenough, Angela K" uniqKey="Goodenough A" first="Angela K." last="Goodenough">Angela K. Goodenough</name><name sortKey="Guengerich, F Peter" sort="Guengerich, F Peter" uniqKey="Guengerich F" first="F. Peter" last="Guengerich">F. Peter Guengerich</name><name sortKey="Kozekov, Ivan D" sort="Kozekov, Ivan D" uniqKey="Kozekov I" first="Ivan D." last="Kozekov">Ivan D. Kozekov</name><name sortKey="Rizzo, Carmelo J" sort="Rizzo, Carmelo J" uniqKey="Rizzo C" first="Carmelo J." last="Rizzo">Carmelo J. Rizzo</name><name sortKey="Zang, Hong" sort="Zang, Hong" uniqKey="Zang H" first="Hong" last="Zang">Hong Zang</name></country><country name="États-Unis"><region name="État de New York"><name sortKey="Goodenough, Angela K" sort="Goodenough, Angela K" uniqKey="Goodenough A" first="Angela K." last="Goodenough">Angela K. Goodenough</name></region><name sortKey="Guengerich, F Peter" sort="Guengerich, F Peter" uniqKey="Guengerich F" first="F. Peter" last="Guengerich">F. Peter Guengerich</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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