Show simple item record

dc.contributor.author
Guza, Rebecca
dc.contributor.author
Kotandeniya, Delshanee
dc.contributor.author
Murphy, Kristopher
dc.contributor.author
Dissanayake, Thakshila
dc.contributor.author
Lin, Chen
dc.contributor.author
Giambasu, George M.
dc.contributor.author
Lad, Rahul R.
dc.contributor.author
Wojciechowski, Filip
dc.contributor.author
Amin, Shantu
dc.contributor.author
Sturla, Shana J.
dc.contributor.author
Hudson, Robert H.E.
dc.contributor.author
York, Darrin M.
dc.contributor.author
Jankowiak, Ryszard
dc.contributor.author
Jones, Roger
dc.contributor.author
Tretyakova, Natalia Y.
dc.date.accessioned
2019-04-02T12:06:45Z
dc.date.available
2017-06-09T11:43:46Z
dc.date.available
2019-04-02T12:06:45Z
dc.date.issued
2011-05
dc.identifier.issn
1362-4962
dc.identifier.issn
0305-1048
dc.identifier.issn
1362-4954
dc.identifier.other
10.1093/nar/gkq1341
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/36773
dc.identifier.doi
10.3929/ethz-b-000036773
dc.description.abstract
Endogenous 5-methylcytosine (MeC) residues are found at all CG dinucleotides of the p53 tumor suppressor gene, including the mutational ‘hotspots’ for smoking induced lung cancer. MeC enhances the reactivity of its base paired guanine towards carcinogenic diolepoxide metabolites of polycyclic aromatic hydrocarbons (PAH) present in cigarette smoke. In the present study, the structural basis for these effects was investigated using a series of unnatural nucleoside analogs and a representative PAH diolepoxide, benzo[a]pyrene diolepoxide (BPDE). Synthetic DNA duplexes derived from a frequently mutated region of the p53 gene (5′-CCCGGCACCC GC[15N3,13C1-G]TCCGCG-3′, + strand) were prepared containing [15N3, 13C1]-guanine opposite unsubstituted cytosine, MeC, abasic site, or unnatural nucleobase analogs. Following BPDE treatment and hydrolysis of the modified DNA to 2′-deoxynucleosides, N2-BPDE-dG adducts formed at the [15N3, 13C1]-labeled guanine and elsewhere in the sequence were quantified by mass spectrometry. We found that C-5 alkylcytosines and related structural analogs specifically enhance the reactivity of the base paired guanine towards BPDE and modify the diastereomeric composition of N2-BPDE-dG adducts. Fluorescence and molecular docking studies revealed that 5-alkylcytosines and unnatural nucleobase analogs with extended aromatic systems facilitate the formation of intercalative BPDE–DNA complexes, placing BPDE in a favorable orientation for nucleophilic attack by the N2 position of guanine.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Oxford University Press
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc/2.5/
dc.title
Influence of C-5 substituted cytosine and related nucleoside analogs on the formation of benzo[a]pyrene diol epoxide-dG adducts at CG base pairs of DNA
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial 2.5 Generic
dc.date.published
2011-01-17
ethz.journal.title
Nucleic Acids Research
ethz.journal.volume
39
en_US
ethz.journal.issue
9
en_US
ethz.journal.abbreviated
Nucleic Acids Res.
ethz.pages.start
3988
en_US
ethz.pages.end
4006
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
000038633
ethz.publication.place
Oxford
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::03853 - Sturla, Shana / Sturla, Shana
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::03853 - Sturla, Shana / Sturla, Shana
ethz.date.deposited
2017-06-09T11:44:06Z
ethz.source
ECIT
ethz.identifier.importid
imp59364e2cd39b830636
ethz.ecitpid
pub:58754
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-13T06:30:08Z
ethz.rosetta.lastUpdated
2019-04-02T12:07:05Z
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Influence%20of%20C-5%20substituted%20cytosine%20and%20related%20nucleoside%20analogs%20on%20the%20formation%20of%20benzo%5Ba%5Dpyrene%20diol%20epoxide-dG%20adducts%20at%&rft.jtitle=Nucleic%20Acids%20Research&rft.date=2011-05&rft.volume=39&rft.issue=9&rft.spage=3988&rft.epage=4006&rft.issn=1362-4962&0305-1048&1362-4954&rft.au=Guza,%20Rebecca&Kotandeniya,%20Delshanee&Murphy,%20Kristopher&Dissanayake,%20Thakshila&Lin,%20Chen&rft.genre=article&
 Search via SFX

Files in this item

Thumbnail

Publication type

Show simple item record