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Calculation of the stabilization energy when the oxidative guanine damages pair with guanine
Published: 25 October 2011 by MDPI in The 15th International Electronic Conference on Synthetic Organic Chemistry session Computational Chemistry
Abstract: The genome DNA is constantly exposed to endogenous and exogenous oxidative stresses. Damaged DNA can cause mutations, which may increase the risk of developing cancer, aging, and other diseases. Various oxidative stresses lead to G:C–T:A and G:C–C:G transversions, because guanine is highly susceptible to oxidative stress in the DNA, owing to the lowest oxidation potential among four nucleobases. One typical lesion product of guanine is 8-oxo-7,8-dihydroguanine (8oxoG), and DNA polymerases incorporate adenine but not guanine opposite 8oxoG lesions. More specifically, 8oxoG:A base pairs cause G:C–T:A transversions, and then the other oxidative guanine damages seem to cause G:C–C:G transversions. 2,5-diamino-4H-imidazol-4-one (Iz) and 2,2,4-triamino-5(2H)-oxazolone (Oz) are the oxidative guanine damages, which can pair with guanine, and several DNA polymerases incorporate guanine opposite these lesions in vitro. We previously reported that the calculated stabilization energy of Iz:G base pair is similar to that of C:G base pair and that of Oz:G base pair is planar and has two hydrogen bonds. Guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) are the oxidative products of 8oxoG. It was shown that Klenow fragment incorporated adenine and guanine opposite these lesions. Our previous study proposed Gh:G and Sp:G base pairs, however, the stabilization energy of these base pairs have not been calculated. Therefore, We estimated the stabilization energy of these base pairs by ab initio molecular orbital calculations.
Keywords: hydrogen bond, oxidation product, base pair