Abstract
Ionizing radiation causes DNA double strand breaks, which are the major cause of detrimental effects of radiation. Induction of DNA double strand breaks has been shown to activate DNA damage checkpoint, and ataxia-telangiectasia mutated (ATM) protein plays a central role in the initiation of this pathway. Recently, it has been reported that ionizing radiation-induced chromatin structure induces autophosphorylation of ATM protein at serine 1981, which results in an activation of ATM as a protein kinase. Although autophosphorylation is shown to convert dimeric or oligomeric forms of ATM to monomeric form, it is not clear how change in the chromatin structure induces autophosphorylation of ATM protein. We have examined phosphorylation of ATM protein at serine 1981 in X-irradiated normal human diploid cells using antibodies recognizing phosphorylated ATM protein at serine 1981. Immunofluorescence study demonstrated that ATM was phosphorylated and formed tiny foci immediately after irradiation, but we also found diffuse pattern of ATM phosphorylation over the nucleus. It is suggested that ATM is phosphorylated not only at the sites of DNA double strand breaks but also phosphorylation is induced in DNA double strand breaks independent manner. The possible mechanism will be discussed.
