Mechanistic clues to the mutagenicity of alkylated DNA bases: A theoretical study

A model for targeted substitution mutagenesis during SOS replication of double‐stranded DNA containing cis‐syn cyclobutane thymine dimers

“…DNA synthesis that occurs with the template bases or the incorporated bases in rare tautomeric forms may result in base substitution mutations. Mutational mechanisms based on the occurrence of rare tautomeric bases were proposed for chemical and radiation mutagenesis as well as for spontaneous mutagenesis [Taylor et al, 1969;Dunean and Davies, 1989;Knicker and Drake, 1990;Blake et al, 1991;Danilov et al, 1997]. These models treat mutagenesis as a pure physical-chemical phenomenon.…”

“…As regards the tautomeric theory of mutagenesis, potential curves and the surfaces of the potential energy of hydrogen-bond (H-bond) protons in DNA and model systems were determined [Lowdin, 1969;Clementi et al, 1984;Young et al, 1987;Tolpygo and Grebneva, 1996;Danilov et al, 1997]. Also investigated was the influence of hydration on the equilibrium of bases [Poltev et al, 1995]; the role of rare tautomeric bases in spontaneous mutation [Blake et al, 1991], thermal mutagenesis [Knicker and Drake, 1990], and the mutagenicity of alkylated bases [Dunean and Davies, 1989]; and the role of double-proton phototautomerization of DNA in mutagenesis [Taylor et al, 1969;Danilov et al, 1997]. I have been particularly interested in the contribution of tautomeric state changes in UV mutagenesis [Grebneva, 1994[Grebneva, , 2001b[Grebneva, , 2002a[Grebneva, , 2003, and both experimental and theoretical studies have been conducted on this subject [see Grebneva, 2002aGrebneva, , 2003 and the review articles mentioned therein].…”

Mutagenic role of Watson-Crick protons in alkylated DNA bases: A theoretical study

“…This prompted the need to advance a molecular basis for differentiating between promutagenic and nonmutagenic species. In an earlier paper, Duncan and Davies (1989) had proposed abstraction of the Watson-Crick protons (the N 1 -proton for alkylated guanines and the N 3 -proton for alkylthymines) as a mechanistic basis for the conferring of mutation-inducing properties on to the alkylated base residue.…”

The nature and possible mechanisms of potential mutations formation due to the appearance of tymine dimers after irradiating two-stranded DNA by ultra-violet light

“…Вскоре Левдин предположил, что изменения таутомерных состоя ний могут происходить и в спаренных основаниях ДНК [42]. В результате этого гипотеза Уотсона и Крика получила «второе дыхание» [43], и в даль нейшем участие редких таутомерных форм в мута генезе обсуждалось неоднократно [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][89][90][91][92][93][94][95][96]. Так, роль таутомерных переходов в мутагенности аналогов оснований является уже почти общеприз нанной [44,95].…”

“…Также часто обсуждается вопрос о важной роли редких таутомерных форм в спон танном [46] и тепловом мутагенезе [47]. Предпо лагается важное значение протонирования атомов, участвующих в образовании водородных связей, для механизмов мутагенности алкилированных ос нований [48].…”