MOLECULAR CHARACTERIZATION OF A COMMON FRAGILE SITE (FRA7H) ON HUMAN-CHROMOSOME-7 BY THE CLONING OF A SIMIAN-VIRUS-40 INTEGRATION SITE

Common fragile sites are chromosomal loci prone to breakage and rearra ngement, hypothesized to provide targets for foreign DNA integration. We cloned a simian virus 40 integration site and showed by fluorescent in situ hybridization analysis that the integration event had occurre d within a common aphidicolin-induced fragile site on human chromosome 7, FRA7H. A region of 161 kb spanning FRA7H was defined and sequenced , Several regions with a potential unusual DNA structure, including hi gh-flexibility, low-stability, and non-B-DNA-forming sequences were id entified in this region. We performed a similar analysis on the publis hed FRA3B sequence and the putative partial FRA7G, which also revealed an impressive cluster of regions with high flexibility and low stabil ity. Thus, these unusual DNA characteristics are possibly intrinsic pr operties of common fragile sites that may affect their replication and condensation as well as organization, and may lead to fragility.