| http://purl.uniprot.org/citations/19542228 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19542228 | http://www.w3.org/2000/01/rdf-schema#comment | "Human polymerase kappa (hPol kappa) is one of four eukaryotic Y-class DNA polymerases and may be an important element in the cellular response to polycyclic aromatic hydrocarbons such as benzo[a]pyrene, which can lead to reactive oxygenated metabolite-mediated oxidative stress. Here, we present a detailed analysis of the activity and specificity of hPol kappa bypass opposite the major oxidative adduct 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG). Unlike its archaeal homolog Dpo4, hPol kappa bypasses this lesion in an error-prone fashion by inserting mainly dATP. Analysis of transient-state kinetics shows diminished "bursts" for dATP:8-oxoG and dCTP:8-oxoG incorporation, indicative of non-productive complex formation, but dATP:8-oxoG insertion events that do occur are 2-fold more efficient than dCTP:G insertion events. Crystal structures of ternary hPol kappa complexes with adducted template-primer DNA reveal non-productive (dGTP and dATP) alignments of incoming nucleotide and 8-oxoG. Structural limitations placed upon the hPol kappa by interactions between the N-clasp and finger domains combined with stabilization of the syn-oriented template 8-oxoG through the side chain of Met-135 both appear to contribute to error-prone bypass. Mutating Leu-508 in the little finger domain of hPol kappa to lysine modulates the insertion opposite 8-oxoG toward more accurate bypass, similar to previous findings with Dpo4. Our structural and activity data provide insight into important mechanistic aspects of error-prone bypass of 8-oxoG by hPol kappa compared with accurate and efficient bypass of the lesion by Dpo4 and polymerase eta."xsd:string |
| http://purl.uniprot.org/citations/19542228 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.003905"xsd:string |
| http://purl.uniprot.org/citations/19542228 | http://purl.uniprot.org/core/author | "Eoff R.L."xsd:string |
| http://purl.uniprot.org/citations/19542228 | http://purl.uniprot.org/core/author | "Irimia A."xsd:string |
| http://purl.uniprot.org/citations/19542228 | http://purl.uniprot.org/core/author | "Guengerich F.P."xsd:string |
| http://purl.uniprot.org/citations/19542228 | http://purl.uniprot.org/core/author | "Egli M."xsd:string |
| http://purl.uniprot.org/citations/19542228 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19542228 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/19542228 | http://purl.uniprot.org/core/pages | "22467-22480"xsd:string |
| http://purl.uniprot.org/citations/19542228 | http://purl.uniprot.org/core/title | "Structural and functional elucidation of the mechanism promoting error-prone synthesis by human DNA polymerase kappa opposite the 7,8-dihydro-8-oxo-2'-deoxyguanosine adduct."xsd:string |
| http://purl.uniprot.org/citations/19542228 | http://purl.uniprot.org/core/volume | "284"xsd:string |
| http://purl.uniprot.org/citations/19542228 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19542228 |
| http://purl.uniprot.org/citations/19542228 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19542228 |
| http://purl.uniprot.org/uniprot/#_Q9UBT6-mappedCitation-19542228 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19542228 |
| http://purl.uniprot.org/uniprot/Q9UBT6 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/19542228 |