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http://purl.uniprot.org/citations/19492058http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19492058http://www.w3.org/2000/01/rdf-schema#comment"

Background

Oxygen-free radicals formed during normal aerobic cellular metabolism attack bases in DNA and 7,8-dihydro-8-oxoguanine (8-oxoG) is one of the major lesions formed. It is amongst the most mutagenic lesions in cells because of its dual coding potential, wherein 8-oxoG(syn) can pair with an A in addition to normal base pairing of 8-oxoG(anti) with a C. Human DNA polymerase kappa (Polkappa) is a member of the newly discovered Y-family of DNA polymerases that possess the ability to replicate through DNA lesions. To understand the basis of Polkappa's preference for insertion of an A opposite 8-oxoG lesion, we have solved the structure of Polkappa in ternary complex with a template-primer presenting 8-oxoG in the active site and with dATP as the incoming nucleotide.

Methodology and principal findings

We show that the Polkappa active site is well-adapted to accommodate 8-oxoG in the syn conformation. That is, the polymerase and the bound template-primer are almost identical in their conformations to that in the ternary complex with undamaged DNA. There is no steric hindrance to accommodating 8-oxoG in the syn conformation for Hoogsteen base-paring with incoming dATP.

Conclusions and significance

The structure we present here is the first for a eukaryotic translesion synthesis (TLS) DNA polymerase with an 8-oxoG:A base pair in the active site. The structure shows why Polkappa is more efficient at inserting an A opposite the 8-oxoG lesion than a C. The structure also provides a basis for why Polkappa is more efficient at inserting an A opposite the lesion than other Y-family DNA polymerases."xsd:string
http://purl.uniprot.org/citations/19492058http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0005766"xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/author"Swan M.K."xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/author"Johnson R.E."xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/author"Prakash L."xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/author"Prakash S."xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/author"Vasquez-Del Carpio R."xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/author"Aggarwal A.K."xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/author"Choudhury J.R."xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/author"Lone S."xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/author"Silverstein T.D."xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/pages"e5766"xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/title"Structure of human DNA polymerase kappa inserting dATP opposite an 8-OxoG DNA lesion."xsd:string
http://purl.uniprot.org/citations/19492058http://purl.uniprot.org/core/volume"4"xsd:string
http://purl.uniprot.org/citations/19492058http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19492058
http://purl.uniprot.org/citations/19492058http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19492058
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http://purl.uniprot.org/uniprot/#_P15927-mappedCitation-19492058http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19492058
http://purl.uniprot.org/uniprot/#_P40937-mappedCitation-19492058http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19492058
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http://purl.uniprot.org/uniprot/#_O60673-mappedCitation-19492058http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19492058