Intercalating Polycyclic Aromatic Hydrocarbon−DNA Adducts Poison DNA Religation by Vaccinia Topoisomerase and Act as Roadblocks to Digestion by Exonuclease III†
Identifieur interne : 002D74 ( Main/Exploration ); précédent : 002D73; suivant : 002D75Intercalating Polycyclic Aromatic Hydrocarbon−DNA Adducts Poison DNA Religation by Vaccinia Topoisomerase and Act as Roadblocks to Digestion by Exonuclease III†
Auteurs : Lyudmila Yakovleva [États-Unis] ; Christopher J. Handy [États-Unis] ; Haruhiko Yagi [États-Unis] ; Jane M. Sayer [États-Unis] ; Donald M. Jerina [États-Unis] ; Stewart Shuman [États-Unis]Source :
- Biochemistry [ 0006-2960 ] ; 2006.
Abstract
Polycyclic aromatic hydrocarbon (PAH)−DNA adducts pervert the execution or fidelity of enzymatic DNA transactions and cause mutations and cancer. Here, we examine the effects of intercalating PAH−DNA adducts on the religation reaction of vaccinia DNA topoisomerase, a prototypal type IB topoisomerase (TopIB), and the 3‘ end-resection reaction of Escherichia coli exonuclease III (ExoIII), a DNA repair enzyme. Vaccinia TopIB forms a covalent DNA-(3‘-phosphotyrosyl)-enzyme intermediate at a target site 5‘-C+5C+4C+3T+2T+1p↓N-1 in duplex DNA. The rate of the forward cleavage reaction is suppressed to varying degrees by benzo[a]pyrene (BP) or benzo[c]phenanthrene (BPh) adducts at purine bases within the 3‘-G+5G+4G+3A+2A+1T-1A-2 sequence of the nonscissile strand. We report that BP adducts at the +1 and −2 N6-deoxyadenosine (dA) positions flanking the scissile phosphodiester slow the rate of DNA religation to a greater degree than they do the cleavage rate. By increasing the cleavage equilibrium constant ≥10-fold, the BPdA adducts, which are intercalated via the major groove, act as TopIB poisons. With respect to ExoIII, we find that (i) single BPdA adducts act as durable roadblocks to ExoIII digestion, which is halted at sites 1 and 2 nucleotides prior to the modified base; (ii) single BPhdA adducts, which also intercalate via the major groove, elicit a transient pause prior to the lesion, which is eventually resected; and (iii) BPh adducts at N2-deoxyguanosine, which intercalate via the minor groove, are durable impediments to ExoIII digestion. These results highlight the sensitivity of repair outcomes to the structure of the PAH ring system and whether intercalation occurs via the major or minor groove.
Url:
DOI: 10.1021/bi060158h
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 000A55
- to stream Istex, to step Curation: 000A55
- to stream Istex, to step Checkpoint: 000949
- to stream Main, to step Merge: 002E04
- to stream Main, to step Curation: 002D74
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Intercalating Polycyclic Aromatic Hydrocarbon−DNA Adducts Poison DNA Religation by Vaccinia Topoisomerase and Act as Roadblocks to Digestion by Exonuclease III†</title><author><name sortKey="Yakovleva, Lyudmila" sort="Yakovleva, Lyudmila" uniqKey="Yakovleva L" first="Lyudmila" last="Yakovleva">Lyudmila Yakovleva</name></author><author><name sortKey="Handy, Christopher J" sort="Handy, Christopher J" uniqKey="Handy C" first="Christopher J." last="Handy">Christopher J. Handy</name></author><author><name sortKey="Yagi, Haruhiko" sort="Yagi, Haruhiko" uniqKey="Yagi H" first="Haruhiko" last="Yagi">Haruhiko Yagi</name></author><author><name sortKey="Sayer, Jane M" sort="Sayer, Jane M" uniqKey="Sayer J" first="Jane M." last="Sayer">Jane M. Sayer</name></author><author><name sortKey="Jerina, Donald M" sort="Jerina, Donald M" uniqKey="Jerina D" first="Donald M." last="Jerina">Donald M. Jerina</name></author><author><name sortKey="Shuman, Stewart" sort="Shuman, Stewart" uniqKey="Shuman S" first="Stewart" last="Shuman">Stewart Shuman</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:37C6547076AF880A343DE77212DC96C9EA2CEB02</idno><date when="2006" year="2006">2006</date><idno type="doi">10.1021/bi060158h</idno><idno type="url">https://api.istex.fr/ark:/67375/TPS-0RJFMFC1-3/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000A55</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000A55</idno><idno type="wicri:Area/Istex/Curation">000A55</idno><idno type="wicri:Area/Istex/Checkpoint">000949</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000949</idno><idno type="wicri:doubleKey">0006-2960:2006:Yakovleva L:intercalating:polycyclic:aromatic</idno><idno type="wicri:Area/Main/Merge">002E04</idno><idno type="wicri:Area/Main/Curation">002D74</idno><idno type="wicri:Area/Main/Exploration">002D74</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Intercalating Polycyclic Aromatic Hydrocarbon−DNA Adducts Poison DNA
Religation by Vaccinia Topoisomerase and Act as Roadblocks to Digestion by
Exonuclease III<ref type="bib" target="#bi060158hAF2">†</ref></title><author><name sortKey="Yakovleva, Lyudmila" sort="Yakovleva, Lyudmila" uniqKey="Yakovleva L" first="Lyudmila" last="Yakovleva">Lyudmila Yakovleva</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10021, and Laboratory of Bioorganic Chemistry,NIDDK, National Institutes of Health, Bethesda</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Handy, Christopher J" sort="Handy, Christopher J" uniqKey="Handy C" first="Christopher J." last="Handy">Christopher J. Handy</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10021, and Laboratory of Bioorganic Chemistry,NIDDK, National Institutes of Health, Bethesda</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Yagi, Haruhiko" sort="Yagi, Haruhiko" uniqKey="Yagi H" first="Haruhiko" last="Yagi">Haruhiko Yagi</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10021, and Laboratory of Bioorganic Chemistry,NIDDK, National Institutes of Health, Bethesda</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Sayer, Jane M" sort="Sayer, Jane M" uniqKey="Sayer J" first="Jane M." last="Sayer">Jane M. Sayer</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10021, and Laboratory of Bioorganic Chemistry,NIDDK, National Institutes of Health, Bethesda</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Jerina, Donald M" sort="Jerina, Donald M" uniqKey="Jerina D" first="Donald M." last="Jerina">Donald M. Jerina</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10021, and Laboratory of Bioorganic Chemistry,NIDDK, National Institutes of Health, Bethesda</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Shuman, Stewart" sort="Shuman, Stewart" uniqKey="Shuman S" first="Stewart" last="Shuman">Stewart Shuman</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10021, and Laboratory of Bioorganic Chemistry,NIDDK, National Institutes of Health, Bethesda</wicri:cityArea></affiliation><affiliation></affiliation><affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Biochemistry</title><title level="j" type="abbrev">Biochemistry</title><idno type="ISSN">0006-2960</idno><idno type="eISSN">1520-4995</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published">2006</date><date type="published">2006</date><biblScope unit="vol">45</biblScope><biblScope unit="issue">24</biblScope><biblScope unit="page" from="7644">7644</biblScope><biblScope unit="page" to="7653">7653</biblScope></imprint><idno type="ISSN">0006-2960</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-2960</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Polycyclic aromatic hydrocarbon (PAH)−DNA adducts pervert the execution or fidelity of enzymatic DNA transactions and cause mutations and cancer. Here, we examine the effects of intercalating PAH−DNA adducts on the religation reaction of vaccinia DNA topoisomerase, a prototypal type IB topoisomerase (TopIB), and the 3‘ end-resection reaction of Escherichia coli exonuclease III (ExoIII), a DNA repair enzyme. Vaccinia TopIB forms a covalent DNA-(3‘-phosphotyrosyl)-enzyme intermediate at a target site 5‘-C+5C+4C+3T+2T+1p↓N-1 in duplex DNA. The rate of the forward cleavage reaction is suppressed to varying degrees by benzo[a]pyrene (BP) or benzo[c]phenanthrene (BPh) adducts at purine bases within the 3‘-G+5G+4G+3A+2A+1T-1A-2 sequence of the nonscissile strand. We report that BP adducts at the +1 and −2 N6-deoxyadenosine (dA) positions flanking the scissile phosphodiester slow the rate of DNA religation to a greater degree than they do the cleavage rate. By increasing the cleavage equilibrium constant ≥10-fold, the BPdA adducts, which are intercalated via the major groove, act as TopIB poisons. With respect to ExoIII, we find that (i) single BPdA adducts act as durable roadblocks to ExoIII digestion, which is halted at sites 1 and 2 nucleotides prior to the modified base; (ii) single BPhdA adducts, which also intercalate via the major groove, elicit a transient pause prior to the lesion, which is eventually resected; and (iii) BPh adducts at N2-deoxyguanosine, which intercalate via the minor groove, are durable impediments to ExoIII digestion. These results highlight the sensitivity of repair outcomes to the structure of the PAH ring system and whether intercalation occurs via the major or minor groove.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Yakovleva, Lyudmila" sort="Yakovleva, Lyudmila" uniqKey="Yakovleva L" first="Lyudmila" last="Yakovleva">Lyudmila Yakovleva</name></region><name sortKey="Handy, Christopher J" sort="Handy, Christopher J" uniqKey="Handy C" first="Christopher J." last="Handy">Christopher J. Handy</name><name sortKey="Jerina, Donald M" sort="Jerina, Donald M" uniqKey="Jerina D" first="Donald M." last="Jerina">Donald M. Jerina</name><name sortKey="Sayer, Jane M" sort="Sayer, Jane M" uniqKey="Sayer J" first="Jane M." last="Sayer">Jane M. Sayer</name><name sortKey="Shuman, Stewart" sort="Shuman, Stewart" uniqKey="Shuman S" first="Stewart" last="Shuman">Stewart Shuman</name><name sortKey="Yagi, Haruhiko" sort="Yagi, Haruhiko" uniqKey="Yagi H" first="Haruhiko" last="Yagi">Haruhiko Yagi</name></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 002D74 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002D74 | 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= ISTEX:37C6547076AF880A343DE77212DC96C9EA2CEB02
|texte= Intercalating Polycyclic Aromatic Hydrocarbon−DNA Adducts Poison DNA Religation by Vaccinia Topoisomerase and Act as Roadblocks to Digestion by Exonuclease III†
}}
| This area was generated with Dilib version V0.6.33. |  |