ATM autophosphorylation

The ATM protein is a key signaling kinase that is activated by DNA damage and ionizing radiation. In the January 30 Nature, Christopher Bakkenist and Michael Kastan at St Jude Children's Research Hospital, Tennessee, USA, describe a novel mechanism by which ATM is maintained in the inactive state in normal cells and becomes activated in response to cellular radiation (Nature, 421:499-505, January 30, 2003).

Bakkenist and Kastan observed that ATM becomes phosphorylated in response to ionizing radiation and identified serine 1981 as the phosphorylated residue. They generated polyclonal antibodies that recognized the phosphorylated serine to define the kinetics of ATM activation. ATM is phosphorylated as early as 5 minutes after irradiation and is sensitive to levels as low as 0.1 Gy which generates around 4 double-strand breaks in the genome. In normal cells ATM is held in an inactive dimer in which the ATM kinase domain is bound to the ...