Structural and dynamic effects of single 7-hydro-8-oxoguanine bases located in a frameshift target DNA sequence.
Biophys Chem
; 118(1): 31-41, 2005 Oct 22.
Article
en En
| MEDLINE
| ID: mdl-16039038
DNA 7-hydro-8-oxoguanine (8-oxoG) is implicated in frameshift formation in an G(6) 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 G(6) 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 (exo(-)) DNA polymerase.
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Banco de datos:
MEDLINE
Asunto principal:
ADN
/
Replicación del ADN
/
Guanina
/
Conformación de Ácido Nucleico
Idioma:
En
Revista:
Biophys Chem
Año:
2005
Tipo del documento:
Article
País de afiliación:
Italia