1ht4
From Proteopedia
(New page: 200px<br /><applet load="1ht4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ht4" /> '''SOLUTION STRUCTURE OF A BISTRAND ABASIC SITE...) |
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| - | [[Image:1ht4.gif|left|200px]]<br /><applet load="1ht4" size=" | + | [[Image:1ht4.gif|left|200px]]<br /><applet load="1ht4" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ht4" /> | caption="1ht4" /> | ||
'''SOLUTION STRUCTURE OF A BISTRAND ABASIC SITE LESION STAGGERED IN A 3'-ORIENTATION.'''<br /> | '''SOLUTION STRUCTURE OF A BISTRAND ABASIC SITE LESION STAGGERED IN A 3'-ORIENTATION.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A unique characteristic of ionizing radiation and radiomimetic anticancer | + | 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== | ==About this Structure== | ||
| - | 1HT4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 1HT4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HT4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Lin, Z.]] | [[Category: Lin, Z.]] | ||
| - | [[Category: Santos, C | + | [[Category: Santos, C de los.]] |
[[Category: abasic sites]] | [[Category: abasic sites]] | ||
[[Category: clustered lesions]] | [[Category: clustered lesions]] | ||
[[Category: double helix]] | [[Category: double helix]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:04:34 2008'' |
Revision as of 11:04, 21 February 2008
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SOLUTION STRUCTURE OF A BISTRAND ABASIC SITE LESION STAGGERED IN A 3'-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
1HT4 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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