1HT7

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

Summary for 1HT7

• Entry DOI: 10.2210/pdb1ht7/pdb
• Related: 1HT4
• Descriptor: 5'-D(*CP*GP*CP*AP*TP*GP*(3DR)P*GP*TP*AP*CP*GP*C)-3', 5'-D(*GP*CP*GP*TP*AP*(3DR)P*AP*CP*AP*TP*GP*CP*G)-3' (2 entities in total)
• Functional Keywords: double helix, abasic sites, clustered damage, extruded residues., dna
• Total number of polymer chains: 2
• Total formula weight: 7711.00

Authors

Lin, Z.,de los Santos, C. (deposition date: 2000-12-29, release date: 2001-05-02, Last modification date: 2024-05-22)

Primary citation

Lin, Z.,de los Santos, C.
NMR characterization of clustered bistrand abasic site lesions: effect of orientation on their solution structure.
J.Mol.Biol., 308:341-352, 2001

PubMed 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 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.

PubMed: 11327771
DOI: 10.1006/jmbi.2001.4587

Experimental method

SOLUTION NMR