Kinetics of DSB rejoining and formation of simple chromosome exchange aberrations

Citation
Fa. Cucinotta et al., Kinetics of DSB rejoining and formation of simple chromosome exchange aberrations, INT J RAD B, 76(11), 2000, pp. 1463-1474
Citations number
57
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Experimental Biology
Journal title
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
ISSN journal
0955-3002 → ACNP
Volume
76
Issue
11
Year of publication
2000
Pages
1463 - 1474
Database
ISI
SICI code
0955-3002(200011)76:11<1463:KODRAF>2.0.ZU;2-W
Abstract
Purpose : To investigate the role of kinetics in the processing of DNA doub le strand breaks (DSB), and the formation of simple chromosome exchange abe rrations following X-ray exposures to mammalian cells based on an enzymatic approach. Methods: Using computer simulations based on a biochemical approach, rate-e quations that describe the processing of DSB through the formation of a DNA -enzyme complex were formulated. A second model that allows for competition between two processing pathways was also formulated. The formation of simp le exchange aberrations was modelled as misrepair during the recombination of single DSB with undamaged DNA. Non-linear coupled differential equations corresponding to biochemical pathways were solved numerically by fitting t o experimental data. Results: When mediated by a DSB-repair enzyme complex, the processing of si ngle DSB showed a complex behaviour that gives the appearance of fast and s low components of rejoining. This is due to the time-delay caused by the ac tion time of enzymes in biomolecular reactions. It is shown that the kineti c- and dose-responses of simple chromosome exchange aberrations are well de scribed by a recombination model of DSB interacting with undamaged DNA when aberration formation increases with linear dose-dependence. Competition be tween two or more recombination processes is shown to lead to the formation of simple exchange aberrations with a dose-dependence similar to that of a linear-quadratic model. Conclusions : Using a minimal number of assumptions, the kinetics and dose- response observed experimentally for DSB rejoining and the formation of sim ple chromosome exchange aberrations are shown to be consistent with kinetic models based on enzymatic reaction approaches. A non-linear dose-response for simple exchange aberrations is possible in a model of recombination of DNA containing a DSB with undamaged DNA when two or more pathways compete f or DSB repair.