NMR solution structure of DNA featuring clustered 2'-deoxyribonolactone and 8-oxoguanine lesions.
NMR solution structure of DNA featuring clustered 2'-deoxyribonolactone and 8-oxoguanine lesions.
Biochemistry. 2016 Jun 20;
Authors: Zalesak J, Constant JF, Jourdan M
Abstract
Ionizing radiations, free radicals and reactive oxygen species lead to hundreds of different DNA lesions. Clustered lesions are typical for ionizing radiations. They compromise the efficiency of the base excision repair pathway (BER) and as a consequence, they are much more toxic and mutagenic than isolated lesions. Despite their biological relevance, e.g. in cancer radiotherapy and accidental exposure, they are not very well studied from a structural point of view. And while insights provided by structural studies participate in the understanding of the repair process, only three NMR studies of DNA containing clusters of lesions were reported. Herein, we report the first NMR solution structure of two DNA containing a bistranded cluster with two lesions, the 2'-deoxyribonolactone and 8-oxoguanine lesions. Both DNA duplexes feature a 2'-deoxyribonolactone site in the middle of the sequence of one strand and differ by the relative position of the 8-oxoguanine, staggered 3' or 5' side on the complementary strand at a three nucleotide distance. Depending on its relative position, the repair of the 8-oxoguanine lesion by the base excision repair protein Fpg is either almost complete or inhibited. We found that the structure of the two DNA containing a bistranded cluster of two lesions are similar and do not deviate very much from the standard B-form. As no obvious structural deformations were observed between the two duplexes, we concluded that the differences in Fpg activity are not due to differences in their global conformation.
PMID: 27322640 [PubMed - as supplied by publisher]
More...