| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 9573323 | Biophysical Chemistry | 2005 | 11 Pages |
Abstract
DNA 7-hydro-8-oxoguanine (8-oxoG) is implicated in frameshift formation in an G6 sequence of the HPRT gene in mismatch repair (MMR) defective cells. Using oligonucleotides based on this frameshift hotspot, we investigated how a single 8-oxoG modified the structural and dynamic properties of the G6 tract. A 30 ns molecular dynamics (MD) simulation indicated compression of the minor groove in the immediate vicinity of the lesion. Fluorescence polarization anisotropy (FPA) and MD demonstrated that 8-oxoG increases DNA torsional rigidity and also constrains the movement of the single-stranded region at the single/double stranded DNA junction of model DNA replication template/primer. These constraints influenced the efficiency of primer extension by Klenow (exoâ) DNA polymerase.
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Authors
Flavia Barone, Filip Lankas, Nada Spackova, Jiri Sponer, Peter Karran, Margherita Bignami, Filomena Mazzei,