Keywords: 
• AM1 /
• hydroxyl radical /
• adenine /
• transition state /
• DNA modification /
• muta-tion

Abstract: The cross-linking between DNA complementary pair bases is induced by hydroxyl radical pro-duced through the excitation of UV radiation. It is demonstrated in this paper that the essential cause of the gene mutation, is induced by the cross-linking between DNA complementary pair bases. It is different from the mutation induced by carcinogens that the UV radiation can initiate the point mutation of a double hydrogen-bond bonded AT pair to a triple hydrogen-bond bonded GC or CG pair. Which would be closely related to the formation of 2-hydroxyl adenine from adenine under the irradiation with UV rays. A calculation with an advanced semi-empirical molecular orbital theo-ry, AM1, has been undertaken for the free radical hydroxylation on 2- and 8-positions of adenine. It was concluded through this AM1 calculation that both the hydroxylation reactions would proceed through two steps, both reactions with negative enthalpies need only to leap over the small activation energy obstacles. Therefore, both hydroxylation reactions can realize smoothly regardless the con-sideration from thermodynamic or kinetic aspect. Although the existence of 8-hydroxyl-adenine or 8-hydroxylguanine is a mark of the free radical hydroxylation damage, both hydroxylated bases don't induce the genetic mutation in DNA because of the easily repairing for their injuries not on the hy-drogen-bonded small groove. However, the 2-hydroxyl-adenine and its tautomerized isomer in DNA double helix, induce the point mutations of a double hydrogen-bond bonded pair to a triple hydro-gen-bond bonded pair, i.e. the transformation of AT→GC or AT→CG.