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dc.contributor.author
Aloisi, Claudia M.N.
dc.contributor.author
Nilforoushan, Arman
dc.contributor.author
Ziegler, Nathalie
dc.contributor.author
Sturla, Shana J.
dc.date.accessioned
2022-08-03T08:39:08Z
dc.date.available
2020-05-22T02:31:25Z
dc.date.available
2020-05-22T08:47:24Z
dc.date.available
2022-08-03T08:39:08Z
dc.date.issued
2020-04-15
dc.identifier.issn
0002-7863
dc.identifier.issn
1520-5126
dc.identifier.other
10.1021/jacs.9b11746
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/416229
dc.identifier.doi
10.3929/ethz-b-000416229
dc.description.abstract
DNA mutations can result from replication errors due to different forms of DNA damage, including low-abundance DNA adducts induced by reactions with electrophiles. The lack of strategies to measure DNA adducts within genomic loci, however, limits our understanding of chemical mutagenesis. The use of artificial nucleotides incorporated opposite DNA adducts by engineered DNA polymerases offers a potential basis for site-specific detection of DNA adducts, but the availability of effective artificial nucleotides that insert opposite DNA adducts is extremely limited, and furthermore, there has been no report of a quantitative strategy for determining how much DNA alkylation occurs in a sequence of interest. In this work, we synthesized an artificial nucleotide triphosphate that is selectively inserted opposite O6-carboxymethyl-guanine DNA by an engineered polymerase and is required for DNA synthesis past the adduct. We characterized the mechanism of this enzymatic process and demonstrated that the artificial nucleotide is a marker for the presence and location in the genome of O6-carboxymethyl-guanine. Finally, we established a mass spectrometric method for quantifying the incorporated artificial nucleotide and obtained a linear relationship with the amount of O6-carboxymethyl-guanine in the target sequence. In this work, we present a strategy to identify, locate, and quantify a mutagenic DNA adduct, advancing tools for linking DNA alkylation to mutagenesis and for detecting DNA adducts in genes as potential diagnostic biomarkers for cancer prevention.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
American Chemical Society
en_US
dc.rights.uri
http://rightsstatements.org/page/InC-NC/1.0/
dc.title
Sequence-Specific Quantitation of Mutagenic DNA Damage via Polymerase Amplification with an Artificial Nucleotide
en_US
dc.type
Journal Article
dc.rights.license
In Copyright - Non-Commercial Use Permitted
dc.date.published
2020-03-20
ethz.journal.title
Journal of the American Chemical Society
ethz.journal.volume
142
en_US
ethz.journal.issue
15
en_US
ethz.journal.abbreviated
J. Am. Chem. Soc.
ethz.pages.start
6962
en_US
ethz.pages.end
6969
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Single Base Resolution Genome-Wide Maps of DNA Damage to Forecast Mutation Signatures
en_US
ethz.grant
DNA Adduct Molecular Probes: Elucidating the Diet-Cancer Connection at Chemical Resolution
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Washington, DC
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.grant.agreementno
185020
ethz.grant.agreementno
260341
ethz.grant.fundername
SNF
ethz.grant.fundername
EC
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.funderDoi
10.13039/501100000780
ethz.grant.program
Projekte Lebenswissenschaften
ethz.grant.program
FP7
ethz.date.deposited
2020-05-22T02:31:33Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-05-22T08:47:35Z
ethz.rosetta.lastUpdated
2022-03-29T02:09:31Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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