MOLECULAR MECHANISMS OF TRANSITIONS INDUCED BY CYTOSINE
ANALOGUE: COMPARATIVE QUANTUM-CHEMICAL STUDY
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv;
Institute of High Technologies of Taras Shevchenko Kyiv National University, Ukraine;
Using the simplest molecular models at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of the theory it has been shown for the first time that in addition to traditional incorporational errors caused by facilitated (compared with the canonical DNA bases cytosine (Cyt)) tautomerization of 6-(2-deoxy-?-D-ribofuranosyl)-3,4-dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-7-one (DCyt), this mutagen causes the replication errors, increasing one million times the population of mispair Gua·DCyt* (asterisk marked mutagenic tautomer) as compared with mispair Gua·Cyt*. It is also proved that DCyt in addition to traditional incorporational errors also induces similar errors by an additional mechanism – due to a facilitated tautomerization of the wobble base pair Ade·DCyt (compared to the same pair Ade·Cyt) to a mispair Ade·DCyt* which is quasi-isomorphic Watson-Crick base pair. Moreover, the obtained results allowed interpreting non-inconsistently the existing experimental NMR data.
Key words: cytosine analogue, spontaneous point replication and incorporational errors, transitions, DNA mispairs, transition state of tautomerization, intermolecular hydrogen bonds, Baders’ topologycal analysis of the electron density, DFT, MP2.
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