Webba da Silva, Mateus, Noronha, AM, Noll, DM, Miller, PS, Colvin, OM and Gamcsik, MP (2002) Solution Structure of a DNA Duplex Containing Mispair-AlignedN4C-Ethyl-N4C Interstrand Cross-Linked Cytosines†. Biochemistry, 41 . [Journal article]
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The solution structure of an interstrand cross-linked self-complementary oligodeoxynucleotidecontaining directly opposed alkylated N4C-ethyl-N4C cytosine bases was determined by moleculardynamics calculations guided by NMR-derived restraints. The undecamer d(CGAAAC*TTTCG)2, whereC* represents directly opposed alkylated N4C-ethyl-N4C cytosine bases, serves as model for the cytotoxiccross-links formed by bifunctional alkylating agents used in cancer therapy. The structure of the duplexshows the cross-link protruding into the major groove. An increase in the diameter of the DNA at thepseudoplatform formed by the cross-linked residues creates an A-DNA characteristic hole in the centralportion of the DNA. This results in a centrally underwound base step and a number of subsequentoverwinding steps leading to an overall axis bend toward the major groove. The structure shows narrowingof both minor and major grooves in the proximity of the cross-link. The perturbation leads to preferentialintrastrand base stacking, disruption of adjacent canonical (AâT) base pairing, and buckling of base pairs,the extent of which diminishes with progression away from the lesion site. Overall, the distortion inducedby the cross-link spreads over three base pairs on the 5¢- and 3¢-sides of the cross-link.
|Item Type:||Journal article|
|Faculties and Schools:||Faculty of Life and Health Sciences|
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
|Research Institutes and Groups:||Biomedical Sciences Research Institute|
Biomedical Sciences Research Institute > Molecular Medicine
Biomedical Sciences Research Institute > Molecular Medicine > Transcriptional Regulation & Epigenetics
|Deposited By:||Dr Mateus Webba da Silva|
|Deposited On:||03 May 2011 10:45|
|Last Modified:||04 Dec 2012 14:31|
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