Rejoining and misrejoining of radiation-induced chromatin breaks. II. Biophysical Model.
A biophysical model for the kinetics of the formation of radiation-induced chromosome aberrations is developed to account for the recent experimental results obtained with a combination of the premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) techniques. In this model, we consider the broken ends of DNA double-strand breaks (DSBs) to be reactant and make use of the interaction distance hypothesis. The repair/misrepair process between broken ends is suggested to consist of two steps; the first step represents the two break ends approaching each other, and the second step represents the enzymatic processes leading to DNA end-to-end rejoining. Only the second step is reflected in the kinetics observed in experiments using PCC. The model appears to be able to fit existing data for human cells. It is shown that the kinetics of the formation of chromosome aberrations can be explained by a single rate that characterizes both rejoining and misrejoining of DSBs, suggesting that repair and misrepair share the same mechanism. Fast repair (completed in minutes) in a subset of DSBs is suggested as an explanation of the complete exchanges observed with PCC in human lymphocytes immediately after irradiation. The fast repair component seems to be absent in human fibroblasts.
Wu
H
H
NASA Lyndon B. Johnson Space Center, Radiation Biophysics Laboratory, Houston, Texas 77058, USA.
Durante
M
M
George
K
K
Goodwin
E H
EH
Yang
T C
TC
D002460:Cell Line; D002843:Chromatin / Q000502:physiology / Q000528:radiation effects*; D002869:Chromosome Aberrations; D002894:Chromosomes, Human, Pair 4 / Q000528:radiation effects*; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D005347:Fibroblasts / Q000528:radiation effects; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000528:radiation effects; D008433:Mathematics; D008957:Models, Genetic; D008962:Models, Theoretical; D013997:Time Factors
D002843:Chromatin; D004247:DNA