DAMAGE-SENSING MECHANISMS IN HUMAN-CELLS AFTER IONIZING-RADIATION

Human cells have evolved several mechanisms for responding to damage c reated by ionizing radiation. Some of these responses involve the acti vation or suppression of the transcriptional machinery. Other response s involve the downregulation of enzymes, such as topoisomerase I, whic h appear to be necessary for DNA repair or apoptosis. Over the past fi ve years, many studies have established links between DNA damage, acti vation of transcription factors that are coupled to DNA repair mechani sms, increased gene transcription and altered cell cycle regulation to allow for repair or cell death via apoptosis or necrosis. Together th ese factors determine whether a cell will survive with or without carc inogenic consequences. The immediate responses of human cells to ioniz ing radiation, in terms of sensing and responding to damage, are there fore, critical determinants of cell survival and carcinogenesis.