Human common fragile sites FRA2H and FRA7B.

The chromosomes of all analysed individuals show gaps or breaks in specific regions, the common fragile sites (CFS) (n = 100), when the cells are exposed to replication stress or to some DNA-binding compounds. So, they are “normal” features of human genome, but the frequency of their expression is different in different individuals. CFSs cause genetic instability and are frequently involved in mutations in cancer cells. The causes of their fragility are still under investigation. The analysis of the twenty CFSs until now molecularly characterized revealed same shared features: the AT bases richness, the high DNA flexibility and the DNA late replication. In this work we determined the DNA sequence of the CFS FRA2H (2q32.1-q32.2) and of the telomeric fragile site FRA7B (7p22.3-p21.3) using BAC clones and fluorescent in situ hybridization (FISH). The expression of both CFSs is induced by aphidicolin. FRA7B is also inducible by DAPI (4’,6-diamidino-2-phenylindole). We analysed the molecular composition of these two sequences and searched for the presence of DNA helix high flexibility regions. The chromosome bands 2q32.1 and 7p22 are recurrent breakpoints in chromosome abnormalities in different types of neoplasms.