Abstract
The cause of the high variability of human mitochondrial DNA (mtDNA) remains largely unknown. Three mechanisms of mutagenesis that might account for the generation of nucleotide substitutions in mtDNA have been analyzed: deamination of DNA nitrous bases caused by deamination agents, tautomeric proton migration in nitrous bases, and the hydrolysis of the glycoside bond between the nitrous base and carbohydrate residue in nucleotides against the background of the free-radical damage of DNA polymerase γ. Quantum chemical calculations demonstrated that the hydrolysis of the N-glycoside bond is the most probable mechanism; it is especially prominent in the H strand, which remains free during mtDNA replication for a relatively long time. It has also been found that hydrolytic deamination of adenine in single-stranded regions of the H strand is a possible cause of the high frequency of T → C transitions in the mutation spectra of the L-chain of the major mtDNA noncoding region.
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Translated from Molekulyarnaya Biologiya, Vol. 39, No. 5, 2005, pp. 869–877.
Original Russian Text Copyright © 2005 by Kornienko, Malyarchuk.
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Kornienko, I.V., Malyarchuk, B.A. Analysis of Mutation Mechanisms in Human Mitochondrial DNA. Mol Biol 39, 761–768 (2005). https://doi.org/10.1007/s11008-005-0091-z
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DOI: https://doi.org/10.1007/s11008-005-0091-z