Source:http://linkedlifedata.com/resource/pubmed/id/12600213
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2003-2-25
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| pubmed:abstractText |
The effects of bases flanking single bulky lesions derived from the binding of a benzo[a]pyrene 7,8-diol 9,10-epoxide derivative ((+)-7R,8S,9S,10R stereoisomer) to N(2)-guanine (G*) on translesion bypass catalyzed by the Y-family polymerase pol kappa (hDinB1) were examined in vitro. The lesions were positioned near the middle of six different 43-mer 5'-...XG*Y... sequences (X, Y = C, T, or G, with all other bases remaining fixed). The complementary dCTP is preferentially inserted opposite G* in all of the sequences; however, the proportions of other dNTPs inserted varies as a function of X and Y. The dCTP insertion efficiencies, f(ins) = (V(max)/K(m))(ins), are smaller in the XG*Y than in XGY sequences by factors of approximately 50-90 (GG*T and GG*C) or 5000-25000 (TG*G and CG*G). Remarkably, in XG*Y sequences, f(ins) varies by as much as 3 orders of magnitude, being smallest with G flanking the lesions on the 3'-side and highest with G flanking the adducts on the 5'-side. One-step primer extension efficiencies just beyond the lesions (f(ext)) are generally smaller than f(ins) and also depend on base sequence. However, reasonably efficient translesion bypass of the (+)-trans-[BP]-N(2)-dG adducts is observed in all sequences in running-start experiments with full, or nearly full, primer extension being observed under conditions of [dNTP] > K(m). The key features here are the relatively robust values of the kinetic parameters V(max) that are either diminished to a moderate extent or even enhanced in the presence of the (+)-trans-[BP]-N(2)-dG adducts. In contrast to the small effects of the lesions on V(max), the apparent K(m) values are orders of magnitude greater in XG*Y than in the unmodified XGY sequences. Thus the bypass of (+)-trans-[BP]-N(2)-dG adducts under conditions when [dNTP] < K(m) is quite inefficient. These considerations may be of importance in vivo where [dNTP] <or= K(m), and the translesion bypass of the (+)-trans-[BP]-N(2)-dG by pol kappa may be significantly less efficient than in vitro at higher dNTP concentrations. The base sequence-dependent features of translesion bypass are discussed in terms of the possible conformations of the adducts and the known structural features of bypass polymerases.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2'-deoxycytidine 5'-triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/7,8-Dihydro-7,8-dihydroxybenzo(a)pyr...,
http://linkedlifedata.com/resource/pubmed/chemical/Adenine Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Chromosomal Proteins, Non-Histone,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Directed DNA Polymerase,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxycytosine Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyguanine Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Mutagens,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PAPD7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/POLK protein, human
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0006-2960
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
4
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| pubmed:volume |
42
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2456-66
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| pubmed:dateRevised |
2011-10-3
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| pubmed:meshHeading |
pubmed-meshheading:12600213-7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide,
pubmed-meshheading:12600213-Adenine Nucleotides,
pubmed-meshheading:12600213-Base Sequence,
pubmed-meshheading:12600213-Catalysis,
pubmed-meshheading:12600213-Chromosomal Proteins, Non-Histone,
pubmed-meshheading:12600213-DNA Adducts,
pubmed-meshheading:12600213-DNA Damage,
pubmed-meshheading:12600213-DNA Primers,
pubmed-meshheading:12600213-DNA Replication,
pubmed-meshheading:12600213-DNA-Directed DNA Polymerase,
pubmed-meshheading:12600213-Deoxycytosine Nucleotides,
pubmed-meshheading:12600213-Deoxyguanine Nucleotides,
pubmed-meshheading:12600213-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:12600213-Humans,
pubmed-meshheading:12600213-Kinetics,
pubmed-meshheading:12600213-Mutagenesis,
pubmed-meshheading:12600213-Mutagens,
pubmed-meshheading:12600213-Nuclear Proteins,
pubmed-meshheading:12600213-Templates, Genetic
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| pubmed:year |
2003
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| pubmed:articleTitle |
Effects of base sequence context on translesion synthesis past a bulky (+)-trans-anti-B[a]P-N2-dG lesion catalyzed by the Y-family polymerase pol kappa.
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| pubmed:affiliation |
Department of Chemistry, New York University, 31 Washington Place, New York, New York 10003-5180, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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