Reaction of hydroxyl radical with B- and Z-DNA

Up to now the mechanisms of formation of DNA damages by the {center_dot}OH radical attack are only poorly understood. For example, it is not clear if {center_dot}OH radical attack depends on the DNA polymeric structure, if it is sequence specific and to what extent the {center_dot}OH induced base radicals contribute to the formation of frank strand breaks (FSB), mainly due to attack of sugars. It is accepted now that depending on sequence, topological constraints and environmental factors DNA can adopt different forms such as A, B, C, Z double helices, triple and quadruple helices. Since there are large structural differences between the DNA in B- and Z-forms one may expect differences in the {center_dot}OH radical reaction with the two forms as well as differences in the processes subsequent to {center_dot}OH radical attack which lead to strand breakage. The authors have performed a modeling of {center_dot}OH radical attack on DNA in the B- and Z-form and compared the theoretical results with the experimental patterns of strand breakage in B- and Z-DNA. The calculated probabilities of {center_dot}OH radical attack on sugars and bases in DNA of a given sequence and form were compared to the experimental yields of FSB, i.e. revealed inmore » a neutral pH, and alkali revealed breaks (ARB) in B- and Z-DNA irradiated in dilute aqueous solution. The possible mechanism underlying the pathways from {center_dot}OH radical attack to strand breakage are discussed.« less