NMR characterization of clustered bistrand abasic site lesions: effect of orientation on their solution structure

Journal of Molecular Biology
Z Lin, C de los Santos

Abstract

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 wh...Continue Reading

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Citations

Oct 28, 2008·Biochemistry·Raphael D HazelCarlos de Los Santos
Jun 28, 2002·Nucleic Acids Research·Alexandros G GeorgakilasBetsy M Sutherland
Jan 14, 2005·Nucleic Acids Research·Grégory Eot-HoullierEvelyne Sage
May 1, 2007·Nucleic Acids Research·Grégory Eot-HoullierEvelyne Sage
Dec 13, 2016·Free Radical Biology & Medicine·Evelyne Sage, Naoya Shikazono
Sep 29, 2005·Radiation Research·J H MillerM Dupuis
Feb 12, 2009·International Journal of Radiation Biology·Peter O'Neill, Peter Wardman
Sep 22, 2009·The Journal of Physical Chemistry. B·André DallmannNikolaus P Ernsting
Feb 9, 2006·Chemical Reviews·Mark Lukin, Carlos de Los Santos

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