Chromosome healing, telomere capture and mechanisms of radiation-induced chromosome breakage

It is generally assumed that radiation-induced chromosome breaks are the result of a cell's inability to rejoin DNA double-strand breaks (dsb), but the exact mechanisms underlying the failure to rejoin some dsb and the conversion of these lesions into chromosome breaks are poorly understood at present. It has been speculated that the conversion of dsb into chromosome breaks, following exposure of mammalian cells to ionizing radiation, may be mediated by the enzyme telomerase. Telomerase is a reverse transcriptase that has two distinct functions, to replicate pre-existing chromosome ends (telomeres) and to heal broken chromosomes by de novo addition of telomeric sequences directly on to non-telomeric DNA. Alternatively, dsb may be converted into chromosome breaks by a telomerase-independent mechanism termed telomere capture.

To review telomere biology and to examine the significance of chromosome healing and telomere capture mechanisms tor radiation cytogenetics.

The currently available literature suggests that telomere capture may be a more frequent mechanism for stabilization of broken chromosomes in mammalian cells than telomerase-mediated chromosome healing. However, a definitive conclusion must await improvements in the resolution of molecular cytogenetic techniques to a degree which allows telomerase products to be clearly distinguishable from subtelomeric cryptic translocations indicative of telomere capture.