Flanking Sequence Effects on DNA Interstrand Cross-linking Preferences of Diepoxides

Author (Your Name)

Subhashini Srivatsan, Colby College

Date of Award

2001

Document Type

Honors Thesis (Colby Access Only)

Department

Colby College. Chemistry Dept.

Advisor(s)

Julie T. Millard

Second Advisor

Paul G. Greenwood

Third Advisor

Shari U. Dunham

Abstract

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.

Comments

Full-text download restricted to Colby College campus only.

Keywords

FLANKING SEQUENCE EFFECTS, DNA, Diepoxides, interstrand cross-linking

Recommended Citation

Srivatsan, Subhashini, "Flanking Sequence Effects on DNA Interstrand Cross-linking Preferences of Diepoxides" (2001). Honors Theses. Paper 443.
https://digitalcommons.colby.edu/honorstheses/443

Copyright

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