Abstract

Abstract : Chromosomal fragile sites are regions that show non-random breakage when cells are exposed to specific chemical conditions. Common fragile sites are present in all individuals, and the majority are inducible by the DNA polymerase inhibitor aphidicolin. FRAl6D (l6q23.2) and FRA7O (7q3l.2) are two aphidicolin-inducible common fragile sites and frequent deletions have been observed in these two regions in prostate cancer. The goal of this work is to clone and characterize these two fragile site regions and to then determine if there are any genes within these regions that play an important role in prostate cancer development. The research goal in the first year of this proposal was to isolate contains of overlapping large insert clones that cover these two fragile site regions. Clones from these contains would then be used for a Fish-based analysis of aphidicolin-induced breakage in these two regions. A second goal of the first year of this proposal was to generate high resolution pulsed field gel maps of these two fragile site regions. The work in the first year of this proposal will provide the reagents needed for all the subsequent work on these regions, including the identification of genes that reside within or around these two common fragile sites.

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