1ht7: Difference between revisions
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==STRUCTURE OF A DNA DUPLEX CONTAINING A BISTRAND ABASIC SITE LESION STAGGERED IN A 5'-ORIENTATION.== | |||
<StructureSection load='1ht7' size='340' side='right'caption='[[1ht7]]' scene=''> | |||
| | == Structural highlights == | ||
| | <table><tr><td colspan='2'>[[1ht7]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HT7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HT7 FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ht7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ht7 OCA], [https://pdbe.org/1ht7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ht7 RCSB], [https://www.ebi.ac.uk/pdbsum/1ht7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ht7 ProSAT]</span></td></tr> | |||
</table> | |||
''' | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | |||
== | |||
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. | 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. | ||
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<ref>PMID:11327771</ref> | |||
NMR characterization of clustered bistrand abasic site lesions: effect of orientation on their solution structure., Lin Z, de los Santos C | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1ht7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Lin Z]] | |||
[[Category: De los Santos C]] | |||
Latest revision as of 18:39, 29 November 2023
STRUCTURE OF A DNA DUPLEX CONTAINING A BISTRAND ABASIC SITE LESION STAGGERED IN A 5'-ORIENTATION.
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