Chromosomal fragile sites: Mechanisms of cytogenetic expression and pathogenic consequences

Abstract

Chromosomal fragile sites are clearly intriguing structures with important roles in biology. The comparative analysis of different fragile site loci, both within and between different classes, has been particularly instructive of their mechanisms of cytogenetic expression and the pathogenic consequences of their presence on the chromosome. The comparative analysis of different chromosomal fragile sites can provide an insight into the molecular mechanisms responsible for their cytogenic manifestations and their contributions to human pathology. The highly conserved relationships between the distinct classes of fragile sites and their associated genes suggest that normal functional roles are played by these relationships. For the rare, folate sensitive fragile sites, the responsible CCG repeat is invariably located in the 5' untranslated region of the associated gene, suggesting a normal role for these sequences in the RNA. For common fragile sites, FRA3B and FRA16D, the protective function of their respective genes (. FHIT and WWOX/FOR) suggests that these sites and their associated genes are a part of the cell's normal response to environmental conditions that cause replicative stress.