Document Detail

Hidden in plain sight: subtle effects of the 8-oxoguanine lesion on the structure, dynamics, and thermodynamics of a 15-base pair oligodeoxynucleotide duplex.
MedLine Citation:
PMID:  21902242     Owner:  NLM     Status:  MEDLINE    
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.
Charisse M Crenshaw; Jacqueline E Wade; Haribabu Arthanari; Dominique Frueh; Benjamin F Lane; Megan E Núñez
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-08
Journal Detail:
Title:  Biochemistry     Volume:  50     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-28     Completed Date:  2011-12-07     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8463-77     Citation Subset:  IM    
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, United States.
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MeSH Terms
Base Pairing*
Base Sequence
DNA Damage* / drug effects
DNA Repair
Guanine / analogs & derivatives*,  chemical synthesis,  chemistry
Magnetic Resonance Spectroscopy
Oligodeoxyribonucleotides / chemistry*
Grant Support
Reg. No./Substance:
0/Oligodeoxyribonucleotides; 5614-64-2/8-hydroxyguanine; 73-40-5/Guanine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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