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Intrastrand base-stacking buttresses widening of major groovein interstrand cross-linked B-DNA

Webba da Silva, Mateus, Bierbryer, RG, Wilds, CJ, Noronha, AM, Miller, PS and Gamcsik, MP (2005) Intrastrand base-stacking buttresses widening of major groovein interstrand cross-linked B-DNA. Bioorganic & Medicinal Chemistry, 13 . [Journal article]

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DOI: 10.1016/j.bmc.2005.03.032


The introduction of a covalent interstrand cross-link induces changes in the intrinsic structure and deformability of theDNA helix that are recognized by elements of the DNA repair apparatus. In this context, the solution structure of the undecamerd(CGAAAT*TTTCG)2, where T* represents a N3T–butyl–N3T interstrand cross-link, was determined using molecular dynamicscalculations restrained by NOE and dihedral angle data obtained from NMR spectroscopy. The structure of this cross-linked undecamershows dramatic widening of the major groove of the B-DNA stem without disruption of Watson–Crick base pairing. Thischange in tertiary structure illustrates the cumulative effect of cooperativity in intrastrand base stacking of an A-tract of three adenines.Further, it is the direct result from the imposition of geometric angular constraints by the cross-link chain on an ApT* andT*pT steps in the segment AAAT*T. The widening of the major groove is due to the dominant contribution of base stacking to thestability of the ApT compared to the TpT step suggesting that the latter is more deformable within a DNA stem. Compared to earlierstructures of ethyl cross-linked oligonucleotides, this unique perturbation induced by the butyl moiety offers a new probe forsystematic studies of DNA repair mechanisms.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Genomic Medicine
ID Code:18297
Deposited By: Dr Mateus Webba da Silva
Deposited On:03 May 2011 09:57
Last Modified:10 May 2017 10:24

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