Benzo[a]pyrene diol epoxide adducts in DNA are potent suppressors of a normal topoisomerase I cleavage site and powerful inducers of other topoisomerase I cleavages.
Identifieur interne : 003631 ( Main/Exploration ); précédent : 003630; suivant : 003632Benzo[a]pyrene diol epoxide adducts in DNA are potent suppressors of a normal topoisomerase I cleavage site and powerful inducers of other topoisomerase I cleavages.
Auteurs : Y. Pommier [États-Unis] ; G. Kohlhagen ; P. Pourquier ; J M Sayer ; H. Kroth ; D M JerinaSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2000.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : DNA Topoisomerases, Type I, Recombinant Fusion Proteins.
- chemical : 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide, DNA Adducts.
- Animals, Binding Sites, CHO Cells, Cricetinae, Humans, Recombination, Genetic.
Abstract
The catalytic intermediates of DNA topoisomerase I (top1) are cleavage complexes that can relax DNA supercoiling (intramolecular reaction) or mediate recombinations (intermolecular religation). We report here that DNA adducts formed from benzo[a]pyrene bay-region diol epoxides can markedly affect top1 activity. Four oligonucleotide 22-mers of the same sequence were synthesized, each of which contained a stereoisomerically unique benzo[a]pyrene 7, 8-diol 9,10-epoxide adduct at the 2-amino group of a central 2'-deoxyguanosine residue. These four adducts correspond to either cis or trans opening at C-10 of the (+)-(7R, 8S, 9S, 10R)- or (-)-(7S, 8R, 9R, 10S)-7,8-diol 9,10-epoxides. Their solution conformations in duplex DNA (intercalated and minor-groove bound for the cis and trans opened adducts respectively) can be deduced from previous NMR studies. All four adducts completely suppress top1 cleavage activity at the alkylation site and induce the formation of new top1cleavage complexes on both strands of the DNA 3-6 bases away from the alkylation site. The trans opened adduct from the highly carcinogenic (+)-diol epoxide is the most active in inducing top1 cleavage independently of camptothecin, demonstrating that minor groove alkylation can efficiently poison top1. We also found that this isomer of the diol epoxide induces the formation of top1-DNA complexes in mammalian cells, which suggests a possible relationship between induction of top1 cleavage complexes and carcinogenic activity of benzo[a]pyrene diol epoxides.
DOI: 10.1073/pnas.040397497
PubMed: 10688881
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 002598
- to stream PubMed, to step Curation: 002598
- to stream PubMed, to step Checkpoint: 002455
- to stream Ncbi, to step Merge: 000047
- to stream Ncbi, to step Curation: 000047
- to stream Ncbi, to step Checkpoint: 000047
- to stream Main, to step Merge: 003673
- to stream Main, to step Curation: 003631
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Benzo[a]pyrene diol epoxide adducts in DNA are potent suppressors of a normal topoisomerase I cleavage site and powerful inducers of other topoisomerase I cleavages.</title><author><name sortKey="Pommier, Y" sort="Pommier, Y" uniqKey="Pommier Y" first="Y" last="Pommier">Y. Pommier</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Kohlhagen, G" sort="Kohlhagen, G" uniqKey="Kohlhagen G" first="G" last="Kohlhagen">G. Kohlhagen</name></author><author><name sortKey="Pourquier, P" sort="Pourquier, P" uniqKey="Pourquier P" first="P" last="Pourquier">P. Pourquier</name></author><author><name sortKey="Sayer, J M" sort="Sayer, J M" uniqKey="Sayer J" first="J M" last="Sayer">J M Sayer</name></author><author><name sortKey="Kroth, H" sort="Kroth, H" uniqKey="Kroth H" first="H" last="Kroth">H. Kroth</name></author><author><name sortKey="Jerina, D M" sort="Jerina, D M" uniqKey="Jerina D" first="D M" last="Jerina">D M Jerina</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2000">2000</date><idno type="RBID">pubmed:10688881</idno><idno type="pmid">10688881</idno><idno type="doi">10.1073/pnas.040397497</idno><idno type="wicri:Area/PubMed/Corpus">002598</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002598</idno><idno type="wicri:Area/PubMed/Curation">002598</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002598</idno><idno type="wicri:Area/PubMed/Checkpoint">002455</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002455</idno><idno type="wicri:Area/Ncbi/Merge">000047</idno><idno type="wicri:Area/Ncbi/Curation">000047</idno><idno type="wicri:Area/Ncbi/Checkpoint">000047</idno><idno type="wicri:doubleKey">0027-8424:2000:Pommier Y:benzo:a:pyrene</idno><idno type="wicri:Area/Main/Merge">003673</idno><idno type="wicri:Area/Main/Curation">003631</idno><idno type="wicri:Area/Main/Exploration">003631</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Benzo[a]pyrene diol epoxide adducts in DNA are potent suppressors of a normal topoisomerase I cleavage site and powerful inducers of other topoisomerase I cleavages.</title><author><name sortKey="Pommier, Y" sort="Pommier, Y" uniqKey="Pommier Y" first="Y" last="Pommier">Y. Pommier</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Kohlhagen, G" sort="Kohlhagen, G" uniqKey="Kohlhagen G" first="G" last="Kohlhagen">G. Kohlhagen</name></author><author><name sortKey="Pourquier, P" sort="Pourquier, P" uniqKey="Pourquier P" first="P" last="Pourquier">P. Pourquier</name></author><author><name sortKey="Sayer, J M" sort="Sayer, J M" uniqKey="Sayer J" first="J M" last="Sayer">J M Sayer</name></author><author><name sortKey="Kroth, H" sort="Kroth, H" uniqKey="Kroth H" first="H" last="Kroth">H. Kroth</name></author><author><name sortKey="Jerina, D M" sort="Jerina, D M" uniqKey="Jerina D" first="D M" last="Jerina">D M Jerina</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><imprint><date when="2000" type="published">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide</term><term>Animals</term><term>Binding Sites</term><term>CHO Cells</term><term>Cricetinae</term><term>DNA Adducts</term><term>DNA Topoisomerases, Type I (metabolism)</term><term>Humans</term><term>Recombinant Fusion Proteins (metabolism)</term><term>Recombination, Genetic</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>7,8,8a,9a-Tétrahydro-benzo[10,11]chryséno[3,4-b]oxirène-7,8-diol</term><term>ADN topoisomérases de type I (métabolisme)</term><term>Adduits à l'ADN</term><term>Animaux</term><term>Cellules CHO</term><term>Cricetinae</term><term>Humains</term><term>Protéines de fusion recombinantes (métabolisme)</term><term>Recombinaison génétique</term><term>Sites de fixation</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA Topoisomerases, Type I</term><term>Recombinant Fusion Proteins</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide</term><term>DNA Adducts</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ADN topoisomérases de type I</term><term>Protéines de fusion recombinantes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Binding Sites</term><term>CHO Cells</term><term>Cricetinae</term><term>Humans</term><term>Recombination, Genetic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>7,8,8a,9a-Tétrahydro-benzo[10,11]chryséno[3,4-b]oxirène-7,8-diol</term><term>Adduits à l'ADN</term><term>Animaux</term><term>Cellules CHO</term><term>Cricetinae</term><term>Humains</term><term>Recombinaison génétique</term><term>Sites de fixation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The catalytic intermediates of DNA topoisomerase I (top1) are cleavage complexes that can relax DNA supercoiling (intramolecular reaction) or mediate recombinations (intermolecular religation). We report here that DNA adducts formed from benzo[a]pyrene bay-region diol epoxides can markedly affect top1 activity. Four oligonucleotide 22-mers of the same sequence were synthesized, each of which contained a stereoisomerically unique benzo[a]pyrene 7, 8-diol 9,10-epoxide adduct at the 2-amino group of a central 2'-deoxyguanosine residue. These four adducts correspond to either cis or trans opening at C-10 of the (+)-(7R, 8S, 9S, 10R)- or (-)-(7S, 8R, 9R, 10S)-7,8-diol 9,10-epoxides. Their solution conformations in duplex DNA (intercalated and minor-groove bound for the cis and trans opened adducts respectively) can be deduced from previous NMR studies. All four adducts completely suppress top1 cleavage activity at the alkylation site and induce the formation of new top1cleavage complexes on both strands of the DNA 3-6 bases away from the alkylation site. The trans opened adduct from the highly carcinogenic (+)-diol epoxide is the most active in inducing top1 cleavage independently of camptothecin, demonstrating that minor groove alkylation can efficiently poison top1. We also found that this isomer of the diol epoxide induces the formation of top1-DNA complexes in mammalian cells, which suggests a possible relationship between induction of top1 cleavage complexes and carcinogenic activity of benzo[a]pyrene diol epoxides.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><noCountry><name sortKey="Jerina, D M" sort="Jerina, D M" uniqKey="Jerina D" first="D M" last="Jerina">D M Jerina</name><name sortKey="Kohlhagen, G" sort="Kohlhagen, G" uniqKey="Kohlhagen G" first="G" last="Kohlhagen">G. Kohlhagen</name><name sortKey="Kroth, H" sort="Kroth, H" uniqKey="Kroth H" first="H" last="Kroth">H. Kroth</name><name sortKey="Pourquier, P" sort="Pourquier, P" uniqKey="Pourquier P" first="P" last="Pourquier">P. Pourquier</name><name sortKey="Sayer, J M" sort="Sayer, J M" uniqKey="Sayer J" first="J M" last="Sayer">J M Sayer</name></noCountry><country name="États-Unis"><region name="Maryland"><name sortKey="Pommier, Y" sort="Pommier, Y" uniqKey="Pommier Y" first="Y" last="Pommier">Y. Pommier</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003631 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 003631 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:10688881
|texte= Benzo[a]pyrene diol epoxide adducts in DNA are potent suppressors of a normal topoisomerase I cleavage site and powerful inducers of other topoisomerase I cleavages.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:10688881" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |