Base-Pairing Preferences, Physicochemical Properties and Mutational Behaviour of the DNA Lesion 8-Nitroguanine\dagger\. Bhamra, I., Compagnone-Post, P., a O'Neil, I., a Iwanejko, L., Bates, A. D, & Cosstick, R. Nucleic acids research, 40(21):11126–11138, September, 2012. doi abstract bibtex 8-Nitro-2'-deoxyguanosine (8-nitrodG) is a relatively unstable, mutagenic lesion of DNA that is increasingly believed to be associated with tissue inflammation. Due to the lability of the glycosidic bond, 8-nitrodG cannot be incorporated into oligodeoxynucleotides (ODNs) by chemical DNA synthesis and thus very little is known about its physicochemical properties and base-pairing preferences. Here we describe the synthesis of 8-nitro-2'-O-methylguanosine, a ribonucleoside analogue of this lesion, which is sufficiently stable to be incorporated into ODNs. Physicochemical studies demonstrated that 8-nitro-2'-O-methylguanosine adopts a syn conformation about the glycosidic bond; thermal melting studies and molecular modelling suggest a relatively stable syn-8-nitroG$·$anti-G base pair. Interestingly, when this lesion analogue was placed in a primer-template system, extension of the primer by either avian myeloblastosis virus reverse transcriptase (AMV-RT) or human DNA polymerase $β$ (pol $β$), was significantly impaired, but where incorporation opposite 8-nitroguanine did occur, pol $β$ showed a 2:1 preference to insert dA over dC, while AMV-RT incorporated predominantly dC. The fact that no 8-nitroG$·$G base pairing is seen in the primer extension products suggests that the polymerases may discriminate against this pairing system on the basis of its poor geometric match to a Watson-Crick pair.
@article{Bhamra2012,
title = {Base-Pairing Preferences, Physicochemical Properties and Mutational Behaviour of the {{DNA}} Lesion 8-Nitroguanine\{dagger\}},
author = {Bhamra, Inder and {Compagnone-Post}, Patricia and a O'Neil, Ian and a Iwanejko, Lesley and Bates, Andrew D and Cosstick, Richard},
year = {2012},
month = sep,
journal = {Nucleic acids research},
volume = {40},
number = {21},
eprint = {22965127},
eprinttype = {pubmed},
pages = {11126--11138},
issn = {1362-4962},
doi = {10.1093/nar/gks799},
abstract = {8-Nitro-2'-deoxyguanosine (8-nitrodG) is a relatively unstable, mutagenic lesion of DNA that is increasingly believed to be associated with tissue inflammation. Due to the lability of the glycosidic bond, 8-nitrodG cannot be incorporated into oligodeoxynucleotides (ODNs) by chemical DNA synthesis and thus very little is known about its physicochemical properties and base-pairing preferences. Here we describe the synthesis of 8-nitro-2'-O-methylguanosine, a ribonucleoside analogue of this lesion, which is sufficiently stable to be incorporated into ODNs. Physicochemical studies demonstrated that 8-nitro-2'-O-methylguanosine adopts a syn conformation about the glycosidic bond; thermal melting studies and molecular modelling suggest a relatively stable syn-8-nitroG{$\cdot$}anti-G base pair. Interestingly, when this lesion analogue was placed in a primer-template system, extension of the primer by either avian myeloblastosis virus reverse transcriptase (AMV-RT) or human DNA polymerase {$\beta$} (pol {$\beta$}), was significantly impaired, but where incorporation opposite 8-nitroguanine did occur, pol {$\beta$} showed a 2:1 preference to insert dA over dC, while AMV-RT incorporated predominantly dC. The fact that no 8-nitroG{$\cdot$}G base pairing is seen in the primer extension products suggests that the polymerases may discriminate against this pairing system on the basis of its poor geometric match to a Watson-Crick pair.},
pmid = {22965127},
keywords = {\#nosource},
file = {E:\UBCloud\Zotero\storage\274UEQ6L\Bhamra et al. - 2012 - Base-pairing preferences, physicochemical properti.pdf}
}
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Due to the lability of the glycosidic bond, 8-nitrodG cannot be incorporated into oligodeoxynucleotides (ODNs) by chemical DNA synthesis and thus very little is known about its physicochemical properties and base-pairing preferences. Here we describe the synthesis of 8-nitro-2'-O-methylguanosine, a ribonucleoside analogue of this lesion, which is sufficiently stable to be incorporated into ODNs. Physicochemical studies demonstrated that 8-nitro-2'-O-methylguanosine adopts a syn conformation about the glycosidic bond; thermal melting studies and molecular modelling suggest a relatively stable syn-8-nitroG$·$anti-G base pair. Interestingly, when this lesion analogue was placed in a primer-template system, extension of the primer by either avian myeloblastosis virus reverse transcriptase (AMV-RT) or human DNA polymerase $β$ (pol $β$), was significantly impaired, but where incorporation opposite 8-nitroguanine did occur, pol $β$ showed a 2:1 preference to insert dA over dC, while AMV-RT incorporated predominantly dC. 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Due to the lability of the glycosidic bond, 8-nitrodG cannot be incorporated into oligodeoxynucleotides (ODNs) by chemical DNA synthesis and thus very little is known about its physicochemical properties and base-pairing preferences. Here we describe the synthesis of 8-nitro-2'-O-methylguanosine, a ribonucleoside analogue of this lesion, which is sufficiently stable to be incorporated into ODNs. Physicochemical studies demonstrated that 8-nitro-2'-O-methylguanosine adopts a syn conformation about the glycosidic bond; thermal melting studies and molecular modelling suggest a relatively stable syn-8-nitroG{$\\cdot$}anti-G base pair. Interestingly, when this lesion analogue was placed in a primer-template system, extension of the primer by either avian myeloblastosis virus reverse transcriptase (AMV-RT) or human DNA polymerase {$\\beta$} (pol {$\\beta$}), was significantly impaired, but where incorporation opposite 8-nitroguanine did occur, pol {$\\beta$} showed a 2:1 preference to insert dA over dC, while AMV-RT incorporated predominantly dC. The fact that no 8-nitroG{$\\cdot$}G base pairing is seen in the primer extension products suggests that the polymerases may discriminate against this pairing system on the basis of its poor geometric match to a Watson-Crick pair.},\n pmid = {22965127},\n keywords = {\\#nosource},\n file = {E:\\UBCloud\\Zotero\\storage\\274UEQ6L\\Bhamra et al. - 2012 - Base-pairing preferences, physicochemical properti.pdf}\n}\n\n","author_short":["Bhamra, I.","Compagnone-Post, P.","a O'Neil, I.","a Iwanejko, L.","Bates, A. 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