Targeting Holliday Junctions

• Main Author: Hamilton, Christopher
• Format: Others
• Published: ScholarWorks @ Georgia State University 2014
• Subjects: Cruciform binding ligand; Holliday junction; Homologous recombination
• Online Access: http://scholarworks.gsu.edu/chemistry_theses/63; http://scholarworks.gsu.edu/cgi/viewcontent.cgi?article=1062&context=chemistry_theses

Holliday junctions are formed as an intermediate during DNA recombination as the two strands come together. Recombination occurs during meiosis, and also during DNA double strand repair. Trapping this branched intermediate could prevent DNA repair from occurring in cells which would prove beneficial during cancer treatment. There are many enzymes that cleave Holliday junctions. One such enzyme, T7 Endonuclease I, was specifically chosen to detect ligand binding at the core of the junction since its binding and cleavage of cruciforms is well documented. Specialized bifunctional ligands were studied in this project that were designed to bind DNA structures that are held in close proximity to one another. These compounds have two identical binding modules that are connected by a linker of various length and rigidity, with each module binding very weakly; however, when both modules bind the binding affinity is greatly enhanced. The interactions of these compounds with cruciforms are currently being studied.