Date of Graduation

Summer 2012

Degree

Master of Science in Chemistry

Department

Chemistry

Committee Chair

Gary Meints

Keywords

lesion, NMR, DNA repair, DNA, BER, direct repair, uracil, abasic

Subject Categories

Chemistry

Abstract

The Dickerson sequence of self complementary DNA, ds(C-G-C-G-A-A-T-T-C-G-CG)2, has been thoroughly characterized via two-dimensional NMR, as well as other techniques. We have used this sequence as a frame of reference to map chemical shift changes caused by inclusion of a single lesion base. Due to errors in transcription, damage to the DNA, or carcinogenic substances, single base legions such as uracil, etheno-dA, or abasic sites occur and can result in mutagenic or cytotoxic effects. Several damaged Dickerson sequences were analyzed using NMR and the chemical shifts compared to those of the undamaged Dickerson sequence. The sequences studied were two uracil substituted sequences U3 [ds(C-G-U-G-A-A-T-T-C-G-C-G)2] and U9 [ds(CG-C-G-A-A-T-T-U-G-C-G)2], one sequence with an abasic site S5 [ds(C-G-C-G-S-A-TT-C-G-C-G)2], and an etheno substituted sequence edA5 [ds(C-G-C-G-edA-A-T-T-C-GC-G)2]. By mapping the chemical shifts of the damaged DNA sequences and comparing them against the Dickerson sequence, it was possible to determine the impact of the lesion on the chemical shifts. Preliminary results indicate that structural changes manifest locally, primarily at the site of the lesion and its base pairing partner.

Copyright

© Stephen Kramer

Campus Only

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