Structure and dynamics of DNA duplexes containing a cluster of mutagenic 8-oxoguanine and abasic site lesions.

Clustered DNA damage sites are caused by ionizing radiation. They are much more difficult to repair than are isolated single lesions, and their biol. 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 det. whether these effects on repair mechanism could be due to local structural properties within DNA, the authors used 1H NMR spectroscopy and restrained mol. dynamics simulations to elucidate the structures of 3 DNA duplexes contg. 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, formamidopyrimidine-DNA glycosylase (Fpg), was either complete or inhibited. All of the studied damaged DNA duplexes adopted an overall B-form conformation and the damaged residues remained intrahelical. No striking deformations of the DNA chain were obsd. 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 structural features induced by those lesions and provide new insight into the Fpg recognition process. [on SciFinder(R)]

Références

Titre
Structure and dynamics of DNA duplexes containing a cluster of mutagenic 8-oxoguanine and abasic site lesions.
Type de publication
Article de revue
Année de publication
2014
Revue
J. Mol. Biol.
Volume
426
Pagination
1524–1538
ISSN
0022-2836
Soumis le 12 avril 2018