Structure and Dynamics of DNA Duplexes Containing a Cluster of Mutagenic 8-Oxoguanine and Abasic Site Lesions
| Autor: | Muriel Jourdan, Jean-François Constant, Morgane Lourdin, Lumίr Krejčί, Jan Zalesak |
|---|---|
| Přispěvatelé: | Département de Chimie Moléculaire (DCM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Masaryk University [Brno] (MUNI), Département de Chimie Moléculaire - Ingéniérie et Intéractions BioMoléculaires (DCM - I2BM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2014 |
| Předmět: |
0303 health sciences
Guanine Magnetic Resonance Spectroscopy DNA damage Chemistry Mutagenesis DNA Base excision repair 010402 general chemistry 01 natural sciences DNA sequencing 8-Oxoguanine 0104 chemical sciences 03 medical and health sciences chemistry.chemical_compound Biochemistry Structural Biology Biophysics Nucleic Acid Conformation [CHIM]Chemical Sciences AP site Molecular Biology 030304 developmental biology |
| Zdroj: | Journal of Molecular Biology Journal of Molecular Biology, Elsevier, 2014, 426 (7), pp.1524-1538. ⟨10.1016/j.jmb.2013.12.022⟩ |
| ISSN: | 0022-2836 1089-8638 |
| DOI: | 10.1016/j.jmb.2013.12.022 |
| Popis: | International audience; Clustered DNA damage sites are caused by ionizing radiation. They are much more difficult to repair than are isolated single lesions, and their biological outcomes in terms of mutagenesis and repair inhibition are strongly dependent on the type, relative position and orientation of the lesions present in the cluster. To determine whether these effects on repair mechanism could be due to local structural properties within DNA, we used 1H NMR spectroscopy and restrained molecular dynamics simulation to elucidate the structures of three DNA duplexes containing bistranded clusters of lesions. Each DNA sequence contained an abasic site in the middle of one strand and differed by the relative position of the 8-oxoguanine, staggered on either the 3′ or the 5′ side of the complementary strand. Their repair by base excision repair protein Fpg was either complete or inhibited. All the studied damaged DNA duplexes adopt an overall B-form conformation and the damaged residues remain intrahelical. No striking deformations of the DNA chain have been observed as a result of close proximity of the lesions. These results rule out the possibility that differential recognition of clustered DNA lesions by the Fpg protein could be due to changes in the DNA's structural features induced by those lesions and provide new insight into the Fpg recognition process. |
| Databáze: | OpenAIRE |
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