Mechanisms of formation of targeted deletions in the synthesis of DNA molecule containing cis-syn cyclobutane thymine dimers
DOI:
https://doi.org/10.15407/dopovidi2015.04.123Keywords:
DNA, molecule, synthesis, targeted deletions, thymine dimersAbstract
In the frame of author’s polymerase-tautomer model of ultraviolet mutagenesis, a mechanism of formation of targeted deletions formation that are caused by cis-syn cyclobutane thymine dimers is proposed. Deletions are frameshift mutations, when one or several nucleotides are dropped out from a DNA strand. Ultraviolet irradiation can result in changes of the tautomer states of DNA bases. A thymine molecule can form 5 rare tautomeric forms. They are stable if these bases are parts of cyclobutane dimers. Structural analysis shows that, opposite the rare tautomeric form of thymine T*2, it is impossible to insert any of the canonical DNA baseswith the formation of hydrogen bonds. It is proposed that, under the synthesis of DNA containing cis-syn cyclobutane thymine dimers TT*2, the specialized or modified DNA polymerases will leave one-nucleotide gaps opposite these cis-syn cyclobutane thymine dimers. The daughter DNA strand opposite cis-syn cyclobutane thymine dimers TT*2 may fall out. If the loop is formed, the daughter strand in the opposite DNA strand will be shortened under the insertion of nucleotides opposite the loop. As an result, some DNA bases are dropped out. The targeted frameshift mutation deletion is formed.
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