1ht7

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1ht7

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STRUCTURE OF A DNA DUPLEX CONTAINING A BISTRAND ABASIC SITE LESION STAGGERED IN A 5'-ORIENTATION.

Overview

A unique characteristic of ionizing radiation and radiomimetic anticancer, drugs is the induction of clustered damage: two or more DNA lesions, (oxidized bases, abasic sites, or strand breaks) occurring in the same or, different strands of the DNA molecule within a single turn of the helix., In spite of arising at a lower frequency than single lesions, clustered, DNA damage represents an exotic challenge to the repair systems present in, the cells and, in some cases, these lesions may escape detection and/or, processing. To understand the structural properties of clustered DNA, lesions we have prepared two oligodeoxynucleotide duplexes containing, adjacent tetrahydrofuran residues (abasic site analogues), positioned one, in each strand of the duplex in a 5' or 3' orientation, and determined, their solution structure by NMR spectroscopy and molecular dynamics, simulations. The NMR data indicate that both duplex structures are, right-handed helices of high similarity outside the clustered damage site., The thermal stability of the duplexes is severely reduced by the presence, of the abasic residues, especially in a 5' orientation where the melting, temperature is 5 degrees C lower. The structures show remarkable, differences at the lesion site where the extrahelical location of the, tetrahydrofuran residues in the (AP)(2)-5'-staggered duplex contrasts with, their smooth alignment along the sugar-phosphate backbone in the, (AP)(2)-3'-staggered duplex.

About this Structure

1HT7 is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

Reference

NMR characterization of clustered bistrand abasic site lesions: effect of orientation on their solution structure., Lin Z, de los Santos C, J Mol Biol. 2001 Apr 27;308(2):341-52. PMID:11327771

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