DNA repair pathways in radiation induced cellular damage: a molecular approach

Abstract

DNA damage, especially double-strand breaks, can be induced by endogenous or exogenous darnaging agents, such as ionizing radiation. Repair of DNA damage is very important in maintaining genomic stability. Incorrect repair may lead to chromosomal aberrations, translocations and deletions. Consequently, incorrect repair might result in oncogenic transformation of cells, which can lead to the development of cancer. Thus, unreaveling the pathways of double-strand break repair is essential in understanding the genetic interactions that lead to ancogen ie changes. Biochemica I studies have provided insight into the molecular mechanisms by which various proteins involved in repair of double-strand breaks perfarm these essential tasks. The next step ahead is analyzing the relationship between the individual biochemical activities of doublestrand break repair proteins and their coordinated action in the context of the living cell. This thesis describes the cellular behaviour and cooperation of the mammalian double-strand break repair genes Rad51, Rad52, Rad54 and Mre11 after induction of DNA damage by ionizing radiation. Furthermore, the possible use for a predictive assay that measures individual radiosensitivity in humans, based on the cellular response to DNA double-strand breaks is examined.