Mechanisms of formation of ionizing radiation-induced chromosomal aberrations: Impact of repair pathways and nuclear architecture (Chromosome Structure), Final report (summary)
Project ID: FIGH-CT-1999-00011Funded under: FP5-EAECTP C
Chromosomal aberrations (CA) contribute to a great extent to hereditary defects and to the development of neoplasms in humans. Ionising radiation (IR) is very efficient in inducing CA in cells both in vitro and in vivo and the analysis of CA is an important approach to assess radiation exposure. To date, molecular cytogenetic techniques have significantly increased the resolution and accuracy of detection and quantification of different types of CA. In this project we aimed at further unravelling the mechanisms of radiation-induced CA. To reach this goal we studied the events occurring from the initial DNA damage, its repair or misrepair and the biological factors influencing the ultimate yield of CA. We employed multicolour FISH and image analysis systems for sensitive detection of CA. Particularly, the project focussed on the impact of chromatin conformation and gene density on induction and repair of IR-induced DNA double strand breaks (DSB) and the role of these factors in the persistence of cancer-related CA. The fast increasing knowledge of the interphase nucleus gives insights in the packaging of chromosomes in territories and their spatial distribution and allows assessing the role of nuclear architecture in the formation of CA. Ultimately, this knowledge will improve our understanding of the interactions leading to CA after exposure to IR. These interactions between chromosomes are strongly influenced by DNA repair pathways and in this project we have assessed the relative contribution of the two major pathways for DSB repair, e.g. non-homologous end joining (NHEJ) and homologous recombination (HR) in the formation of CA. However, the final outcome of CA after IR is not only depending on DNA repair, but is also influenced by two other important defence mechanisms, namely cell cycle checkpoints and apoptosis. Therefore, we included in our study the analysis of the role of cell cycle checkpoints and apoptosis on the yield and types of IR-induced CA.
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Record Number: 8921 / Last updated on: 2008-01-23