GENERATION OF A NEW ADENOVIRUS TYPE 12-INDUCIBLE FRAGILE SITE BY INSERTION OF AN ARTIFICIAL U2 LOCUS IN THE HUMAN GENOME

Infection with adenovirus type 12 (Ad12) induces four fragile sites in the human genome (H. F. Stich, G. L. van Hoosier, and J. J. Trentin, Exp. Cell Res. 34:400-403, 1964; H. zur Hausen, J. Virol. 1:1174-1185, 1967). The major site, at 17q21-22, contains the U2 gene cluster, whi ch is specifically disrupted by infection in at least a percentage of the cells (D. M. Durnam, J. C. Menninger, S. H. Chandler, P. P. Smith, and J. K. McDougall, Mol. Cell. Biol. 8:1863-1867, 1988). For direct assessment of whether the U2 locus is the target of the Ad12 effect, a n artificial locus, constructed in vitro and consisting of tandem arra ys of the U2 6-kbp monomer, was transfected into human cells. We repor t that integration of this artificial locus on the p arm of chromosome 13 creates a new Ad12-inducible fragile site.