Molecular characterization of the human common fragile site FRAIH

The molecular basis of the fragility of common fragile sites (CFS) and their role in chromosome instability and in altered expression of associated genes in cancer cells have not yet been clarified. In the present work we analyzed the human CFS FRAIH. FRAIH is the first characterized CFS the expression of which is not induced by aphiclicolin but instead by DAPI. 5-azaC, 5-azadC, and Ad 12 induce a CFS with the same cytogenetic location. By using FISH analysis with BAC clones, we determined that this CFS extends for approximately 10 Mb, and is therefore one of the largest characterized CFSs. FRAIH maps to the chromosome bands 1q41 and 1q42.1 thus spanning an R-band/G-band boundary, a region considered difficult to duplicate. The FRA I H DNA sequence was analyzed to identify coding sequences, the AT content, the type and quantity of the DNA repeats, the CpG islands, the matrix attachment regions, and the number and distribution of high-flexibility regions. A 120 kb long sequence was identified that is very AT-rich (64.6%), has a very large number of flexibility peaks and that may be involved in inducing fragility in the surrounding regions. Among the other genes, two very large genes (USH2A, ESRRG) and two microRNA genes (MIRN 194-1, MIRN215) map within the fragile region. (c) 2007 Wiley-Liss, Inc.