HEALING OF BROKEN HUMAN-CHROMOSOMES BY THE ADDITION OF TELOMERIC REPEATS

We have characterized and compared a series of naturally occurring chr omosomal truncations involving the terminal region of the short arm of human chromosome 16 (16p13.3). All six broken chromosomes appear to h ave been stabilized by the direct addition of telomeric repeats (TTAGG G)(n) to nontelomeric DNA. In five of the six chromosomes, sequence an alysis shows that the three or four nucleotides preceding the point of telomere addition are complementary to and in phase with the putative RNA template of human telomerase. Otherwise me have found no common s tructural features around the breakpoint regions. These findings, toge ther with previously reported in vitro data, suggest that chromosome-h ealing events in man can be mediated by telomerase and that a small re gion of complementarity to the RNA template of telomerase at the end o f a broken chromosome may be sufficient to prime healing in vivo.