3PA115 Molecular dynamics of thymine base damaged DNA : thymine glycol & thymine dimer : structural and energetic origin of recongition and repair process

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Base flipping of the thymine dimer in duplex DNA.

Exposure of two adjacent thymines in DNA to UV light of 260-320 nm can result in the formation of the cis,syn-cyclobutane pyrimidine dimer (CPD). The structure of DNA containing an intrahelical CPD lesion has been previously studied experimentally and computationally. However, the structure of the extrahelical, flipped-out, CPD lesion, which has been shown to be the structure that binds to the ...

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Dynamics of the excised base release in thymine DNA glycosylase during DNA repair process

Thymine DNA glycosylase (TDG) initiates base excision repair by cleaving the N-glycosidic bond between the sugar and target base. After catalysis, the release of excised base is a requisite step to terminate the catalytic cycle and liberate the TDG for the following enzymatic reactions. However, an atomistic-level understanding of the dynamics of the product release process in TDG remains unkno...

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Direct observation of thymine dimer repair in DNA by photolyase.

Photolyase uses light energy to split UV-induced cyclobutane dimers in damaged DNA, but its molecular mechanism has never been directly revealed. Here, we report the direct mapping of catalytic processes through femtosecond synchronization of the enzymatic dynamics with the repair function. We observed direct electron transfer from the excited flavin cofactor to the dimer in 170 ps and back ele...

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Accuracy of thymine-thymine dimer bypass by Saccharomyces cerevisiae DNA polymerase eta.

The Saccharomyces cerevisiae RAD30 gene functions in error-free replication of UV-damaged DNA. RAD30 encodes a DNA polymerase, Pol eta, which inserts two adenines opposite the two thymines of a cis-syn thymine-thymine (T-T) dimer. Here we use steady-state kinetics to determine the accuracy of DNA synthesis opposite the T-T dimer. Surprisingly, the accuracy of DNA synthesis opposite the damaged ...

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Preferential formation of (5S,6R)-thymine glycol for oligodeoxyribonucleotide synthesis and analysis of drug binding to thymine glycol-containing DNA

We previously reported the chemical synthesis of oligonucleotides containing thymine glycol, a major form of oxidative DNA damage. In the preparation of the phosphoramidite building block, the predominant product of the osmium tetroxide oxidation of protected thymidine was (5R,6S)-thymidine glycol. To obtain the building block of the other isomer, (5S,6R)-thymidine glycol, in an amount sufficie...

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ژورنال

عنوان ژورنال: Seibutsu Butsuri

سال: 1999

ISSN: 0582-4052,1347-4219

DOI: 10.2142/biophys.39.s177_3