HUMAN CHROMOSOMAL FRAGILE SITE FRA16B IS AN AMPLIFIED AT-RICH MINISATELLITE REPEAT

Fragile sites are nonstaining gaps in chromosomes induced by specific tissue culture conditions. They vary both in population frequency and in the culture conditions required for induction. Folate-sensitive fra gile sites are due to expansion of p(CCG)(n) trinucleotide repeats; ho wever, the relationship between sequence composition and the chemistry of induction of fragile sites is unclear. To clarify this relationshi p, the distamycin A-sensitive fragile site FRA16B was isolated by posi tional cloning and found to be an expanded 33 bp AT-rich minisatellite repeat, p(ATATATTATATATTATATCTAATAATATAT(C)/(A)TA)(n) (consistent wit h DNA sequence binding preferences of chemicals that induce its cytoge netic expression). Therefore the mutation mechanism associated with tr inucleotide repeats is also a property of minisatellite repeats (varia ble number tandem repeats).