Date of Award
Honors Thesis (Colby Access Only)
Colby College. Chemistry Dept.
Julie T. Millard
Paul G. Greenwood
Shari U. Dunham
The diepaxyalkanes, a family of DNA damaging agents, exhibit a lower crosslinking efficiency than the nitrogen mustards, despite sharing the same 5'-GNC target sequence for interstrand cross-linking. The cross-linking agents used in this study were diepoxybutane, diepoxyoctane and the nitrogen mustard, mechlorethamine. The main goal in the project was to understand the factors involved in the cross-linking yields of these agents. We used polyacrylamide gel electrophoresis (PAGE), denaturing PAGE, aqueous piperidine cleavage and phosphorimagery to study how flanking sequences around the core 5'-ONC target impact the cross-linking efficiency of diepoxyalkanes relative to mustards. Different synthetic DNA oligomer duplexes containing the sequence [NIGN2CN3Jcontaining each of the four possible bases for N1, N2, and N3 were used. The preliminary data indicated that there may be a preference far thymine as the N] base for diepoxybutane and mechlorethamine, while diepoxyoctane showed a preference for guanine as the N1 base in the core target sequence. This suggests that the flanking sequences may have an effect on the cross-linking efficiency of a DNA cross-linking agent, although these effects vary from agent to agent.
FLANKING SEQUENCE EFFECTS, DNA, Diepoxides, interstrand cross-linking
Recommended CitationSrivatsan, Subhashini, "Flanking Sequence Effects on DNA Interstrand Cross-linking Preferences of Diepoxides" (2001). Honors Theses. Paper 443.
Colby College theses are protected by copyright. They may be viewed or downloaded from this site for the purposes of research and scholarship. Reproduction or distribution for commercial purposes is prohibited without written permission of the author.