ATM-DEPENDENT CELLULAR RESPONSE TO DNA DOUBLE STRAND BREAKS PLAYS A PIVOTAL ROLE IN THE MAINTENANCE OF THE INTEGRITY OF THE GENOME

摘要

ATM-dependent cellular response to DNA double strand breaks plays a pivotal role in the maintenance of the integrity of the genome. Upon irradiation, activated ataxia-telangiectasia mutated (ATM) proteins phosphorylate various downstream mediators and effectors, such as histone H2AX, MDC1, 53BP1 and NBS1. These proteins create discrete foci within the nuclei, which are detectable under fluorescence microscopes. Interestingly, the size of the foci is also increasing as increasing the time after irradiation. Particularly, the residual foci form large foci, the sizes of which reach approximately 2 μm in diameter. We confirmed that such 'foci growth' is a mechanism, by which DNA damage signal is amplified. Especially, a proper DNA damage response of cells to lower doses of ionising radiation required amplification of the ATM-dependent damage signal by recruiting the DNA damage checkpoint factors to the site of chromatin.