THE SIGNAL MODEL - A POSSIBLE EXPLANATION FOR THE CONVERSION OF DNA DOUBLE-STRAND BREAKS INTO CHROMATID BREAKS

Purpose: To present and evaluate the 'signal' model for the formation of radiation-induced chromatid breaks. Conclusions: Chromatid breaks i n human cells represent the apparent interstitial loss of up to about 40 Mbp of DNA, difficult to account for as single lesions under the cl assical 'breakage-and-reunion' hypothesis. If breakage-first resulted from two interacting DNA double-strand breaks (dsb) with the loss or d isplacement of the intervening fragment, a dose-squared relationship w ould be predicted for chromatid breaks. However, the relationship betw een chromatid break frequency and dose for human cells is linear. The alternative 'exchange' model of Revell is based on the principle of th e interaction of two initiating lesions, thus also predicting a dose-s quared relationship for chromatid 'breaks'. The signal model explains the conversion of dsb into chromatid breaks on the assumption that a s ingle dsb generates a signal which triggers the cell to initiate a rec ombinational exchange involving a large loop of chromatin. Incomplete exchanges would he observed as chromatid breaks. Possible candidates f or the signalling molecule(s) are DNA protein kinase (DNA PK) and the ATM protein.