Document Type
Article
Date of Original Version
2006
Department
Biomedical and Pharmaceutical Sciences
Abstract
Circular dichroism (CD) and UV-melting experiments were conducted with 16 oligodeoxynucleotides modified by the carcinogen 2-aminofluorene, whose sequence around the lesion was varied systematically [d(CTTCTNG[AF]NCCTC), N = G, A, C, T], to gain insight into the factors that determine the equilibrium between base-displaced stacked (S) and external B-type (B) duplex conformers. Differing stabilities among the duplexes can be attributed to different populations of S and B conformers. The AF modification always resulted in sequence-dependent thermal (Tm) and thermodynamic (−Δ G °) destabilization. The population of B-type conformers derived from eight selected duplexes (i.e. -AG*N- and -CG*N-) was inversely proportional to the −Δ G ° and Tm values, which highlights the importance of carcinogen/base stacking in duplex stabilization even in the face of disrupted Watson–Crick base pairing in S-conformation. CD studies showed that the extent of the adduct-induced negative ellipticities in the 290–350 nm range is correlated linearly with −Δ G ° and Tm, but inversely with the population of B-type conformations. Taken together, these results revealed a unique interplay between the extent of carcinogenic interaction with neighboring base pairs and the thermodynamic properties of the AF-modified duplexes. The sequence-dependent S/B heterogeneities have important implications in understanding how arylamine–DNA adducts are recognized in nucleotide excision repair.
Citation/Publisher Attribution
Srinivasa Rao Meneni, Rhijuta D'Mello, Gregory Norigian, Gregory Baker, Lan Gao, M. Paul Chiarelli, Bongsup P. Cho; Sequence effects of aminofluorene-modified DNA duplexes: thermodynamic and circular dichroism properties, Nucleic Acids Research, Volume 34, Issue 2, 1 January 2006, Pages 755–763, https://doi.org/10.1093/nar/gkj480
Available at: https://doi.org/10.1093/nar/gkj480