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Effects of DNA Bending on T=C CPD Deamination
Author(s) -
Wang Kesai,
Taylor JohnStephen
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.754.3
Subject(s) - deamination , nucleosome , pyrimidine dimer , histone , dna , chemistry , histone octamer , biophysics , microbiology and biotechnology , dna repair , stereochemistry , biology , biochemistry , enzyme
The cyclobutane pyrimidine dimer (CPD) of a TC site, 1 , is one of the most abundant DNA lesions caused by UVB radiation and has been correlated with C‐to‐T mutations. Unlike T=T CPDs which are stable, the C in C‐containing CPDs readily deaminated to U within hours to days, which then directs the insertion of A during bypass by DNA polymerase eta, resulting in the C to T mutation. In eukaryotic cells, DNA is packaged into nucleosomes, each of which contains 147 bp of DNA wrapped around a histone octamer core, 2 . It has been found that both CPD formation and deamination is greatly inhibited for the sites closest to histone surface and enhanced at outside positions (1). Previous work has shown that bending alone in the absence of the nucleosome can also modulate CPD formation in the same way as in a nucleosome, but it is unknown whether or not deamination is similarly affected by bending or depends more on interaction with the histone proteins. To study the effects of DNA bending on deamination, we designed an 80‐mer circular DNA sequence that we showed modulated TT CPD formation in the same way as a nucleosome, with two TCG sites in outermost and innermost positions respectively. Preliminary results showed no significant difference in deamination rates of the T=CG CPDs, compared to those in free DNA, suggesting that bending alone does not affect deamination. We are currently studying the deamination of TCG CPDs at other rotational positions, both in the nucleosome and in the circular DNA in the event that the positions of the CPDs in the circular DNA were not at the expected innermost and outermost positions. Support or Funding Information This work was supported, in whole or in part, by the National Cancer Institute, National Institutes of Health Grant R01 CA40463 (to J.‐S. T.).