Dissecting the Differences between the α and β Anomers of the Oxidative DNA Lesion FaPydG
2008
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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
21
References
14
Citations
NaN
KQI