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Dissecting the Differences between the α and β Anomers of the Oxidative DNA Lesion FaPydG
Author(s) -
Büsch Florian,
Pieck J. Carsten,
Ober Matthias,
Gierlich Johannes,
Hsu Gerald W.,
Beese Lorena S.,
Carell Thomas
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200701373
Subject(s) - base pair , dna polymerase , oligonucleotide , polymerase , primer (cosmetics) , chemistry , dna , primer extension , stereochemistry , cytidine , anomer , crystallography , biophysics , biochemistry , enzyme , biology , base sequence , organic chemistry
The oxidative DNA lesion, FaPydG rapidly anomerizes to form a mixture of the α and β anomer. To investigate the mutagenic potential of both forms, we prepared stabilized bioisosteric analogues of both configurational isomers and incorporated them into oligonucleotides. These were subsequently used for thermodynamic melting‐point studies and for primer‐extension experiments. While the β compound, in agreement with earlier data, prefers cytidine as the pairing partner, the α compound is not able form a stable base pair with any natural base. In primer‐extension studies with the high‐fidelity polymerase Bst Pol I, the polymerase was able to read through the lesion. The β compound showed no strong mutagenic potential. The α compound, in contrast, strongly destabilized DNA duplexes and also blocked all of the tested DNA polymerases, including two low‐fidelity polymerases of the Y‐family.