Molecular characterization of the human common fragile site FRA1H.
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 FRA1H. FRA1H is the first characterized CFS the expression of which is not induced by aphidicolin but instead by DAPI. 5-azaC, 5-azadC, and Ad12 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. FRA1H maps to the chromosome bands 1q41 and 1q42.1 thus spanning an R-band/G-band boundary, a region considered difficult to duplicate. The FRA1H 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 (MIRN194-1, MIRN215) map within the fragile region.
Curatolo
Angela
A
Dipartimento di Genetica e Biologia Molecolare, Universita, La Sapienza, 00185 Roma, Italia.
Limongi
Zaira M
ZM
Pelliccia
Franca
F
Rocchi
Angela
A
D001483:Base Sequence; D002871:Chromosome Banding; D043283:Chromosome Fragile Sites / Q000235:genetics*; D002874:Chromosome Mapping; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping