Date of Original Version
Biomedical and Pharmaceutical Sciences
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.
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