Adenovirus type 12 (Ad12) infection of human cells induces four chromosomal fragile sites corresponding to the U1 small nuclear RNA (snRNA) genes (the RNU1 locus), the U2 snRNA genes (RNU2), the U1 snRNA pseudogenes (PSU1), and the 5S rRNA genes (RN5S).
Remarkably, we now find that very low doses of actinomycin D (5-50 ng/ml) can phenocopy Ad12 infection: metaphase fragility of the RNU1 and RNU2 loci is induced specifically in the absence of virus, and induction also requires U2 promoter elements and p53 function.