| Hidden in plain sight: subtle effects of the 8-oxoguanine lesion on the structure, dynamics, and thermodynamics of a 15-base pair oligodeoxynucleotide duplex. | |
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MedLine Citation:
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PMID: 21902242 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The base lesion 8-oxoguanine is formed readily by oxidation of DNA, potentially leading to G → T transversion mutations. Despite the apparent similarity of 8-oxoguanine-cytosine base pairs to normal guanine-cytosine base pairs, cellular base excision repair systems effectively recognize the lesion base. Here we apply several techniques to examine a single 8-oxoguanine lesion at the center of a nonpalindromic 15-mer duplex oligonucleotide in an effort to determine what, if anything, distinguishes an 8-oxoguanine-cytosine (8oxoG-C) base pair from a normal base pair. The lesion duplex is globally almost indistinguishable from the unmodified parent duplex using circular dichroism spectroscopy and ultraviolet melting thermodynamics. The DNA mismatch-detecting photocleavage agent Rh(bpy)(2)chrysi(3+) cleaves only weakly and nonspecifically, revealing that the 8oxoG-C pair is locally stable at the level of the individual base pairs. Nuclear magnetic resonance spectra are also consistent with a well-conserved B-form duplex structure. In the two-dimensional nuclear Overhauser effect spectra, base-sugar and imino-imino cross-peaks are strikingly similar between parent and lesion duplexes. Changes in chemical shift due to the 8oxoG lesion are localized to its complementary cytosine and to the 2-3 bp immediately flanking the lesion on the lesion strand. Residues further removed from the lesion are shown to be unperturbed by its presence. Notably, imino exchange experiments indicate that the 8-oxoguanine-cytosine pair is strong and stable, with an apparent equilibrium constant for opening equal to that of other internal guanine-cytosine base pairs, on the order of 10(-6). This collection of experiments shows that the 8-oxoguanine-cytosine base pair is incredibly stable and similar to the native pair. |
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Authors:
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Charisse M Crenshaw; Jacqueline E Wade; Haribabu Arthanari; Dominique Frueh; Benjamin F Lane; Megan E Núñez |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-09-08 |
Journal Detail:
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Title: Biochemistry Volume: 50 ISSN: 1520-4995 ISO Abbreviation: Biochemistry Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-09-28 Completed Date: 2011-12-07 Revised Date: 2013-02-11 |
Medline Journal Info:
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Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: United States |
Other Details:
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Languages: eng Pagination: 8463-77 Citation Subset: IM |
Affiliation:
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Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, United States. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Base Pairing* Base Sequence DNA Damage* / drug effects DNA Repair Guanine / analogs & derivatives*, chemical synthesis, chemistry Magnetic Resonance Spectroscopy Oligodeoxyribonucleotides / chemistry* Thermodynamics |
| Grant Support | |
ID/Acronym/Agency:
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1R15GM083250/GM/NIGMS NIH HHS; R15 GM083250-01/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Oligodeoxyribonucleotides; 5614-64-2/8-hydroxyguanine; 73-40-5/Guanine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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