P E Bryant1. 1. School of Biomedical Sciences, University of St Andrews, Scotland, UK.
Abstract
PURPOSE: To present and evaluate the 'signal' model for the formation of radiation-induced chromatid breaks. CONCLUSIONS: Chromatid breaks in human cells represent the apparent interstitial loss of up to about 40 Mbp of DNA, difficult to account for as single lesions under the classical 'breakage-and-reunion' hypothesis. If breakage-first resulted from two interacting DNA double-strand breaks (dsb) with the loss or displacement of the intervening fragment, a dose-squared relationship would be predicted for chromatid breaks. However, the relationship between chromatid break frequency and dose for human cells is linear. The alternative 'exchange' model of Revell is based on the principle of the interaction of two initiating lesions, thus also predicting a dose-squared relationship for chromatid 'breaks'. The signal model explains the conversion of dsb into chromatid breaks on the assumption that a single dsb generates a signal which triggers the cell to initiate a recombinational exchange involving a large loop of chromatin. Incomplete exchanges would be observed as chromatid breaks. Possible candidates for the signalling molecule(s) are DNA protein kinase (DNA PK) and the ATM protein.
PURPOSE: To present and evaluate the 'signal' model for the formation of radiation-induced chromatid breaks. CONCLUSIONS: Chromatid breaks in human cells represent the apparent interstitial loss of up to about 40 Mbp of DNA, difficult to account for as single lesions under the classical 'breakage-and-reunion' hypothesis. If breakage-first resulted from two interacting DNA double-strand breaks (dsb) with the loss or displacement of the intervening fragment, a dose-squared relationship would be predicted for chromatid breaks. However, the relationship between chromatid break frequency and dose for human cells is linear. The alternative 'exchange' model of Revell is based on the principle of the interaction of two initiating lesions, thus also predicting a dose-squared relationship for chromatid 'breaks'. The signal model explains the conversion of dsb into chromatid breaks on the assumption that a single dsb generates a signal which triggers the cell to initiate a recombinational exchange involving a large loop of chromatin. Incomplete exchanges would be observed as chromatid breaks. Possible candidates for the signalling molecule(s) are DNA protein kinase (DNA PK) and the ATM protein.
Authors: F Zakeri; M R Rajabpour; S A Haeri; R Kanda; I Hayata; S Nakamura; T Sugahara; M J Ahmadpour Journal: Radiat Environ Biophys Date: 2011-09-06 Impact factor: 1.925
Authors: Li-E Wang; Chan H Han; Ping Xiong; Melissa L Bondy; Tse-Kuan Yu; Abenaa M Brewster; Sanjay Shete; Banu K Arun; Thomas A Buchholz; Qingyi Wei Journal: Breast Cancer Res Treat Date: 2012-01-05 Impact factor: 4.872
Authors: Aleksandra M Gorniewska; Katarzyna Kluzek; Lidia Gackowska; Izabela Kubiszewska; Malgorzata Z Zdzienicka; Aneta Bialkowska Journal: Mol Med Rep Date: 2017-06-15 Impact factor: 2.952