Abstract
Cells, which lacked the activity of the nuclease Artemis, retained approximately 10% of unrepaired double strand breaks (DSBs) at later timepoints after ionizing radiation. Ionizing radiation induced hyperphosphorylation of Artemis mainly by ATM and in ATM deficient cells to a minor extent by DNA PK. After induction of DSBs with modified ends by a high dose of calicheamicin ฮณ1, Artemis was phosphorylated by DNA PK. The type of calicheamicin ฮณ1โinduced DSBs is likely to represent a subclass of DSBs induced by ionizing radiation. DNA PKโdependent phosphorylation of Artemis after treatment with DSB inducing agents increased the cellular retention of Artemis, maintained its interaction with DNA ends and activated its endonucleolytic activity. The following model is suggested: ATMโdependent phosphorylation of Artemis after ionizing radiation could prevent DNA PKโdependent phosphorylation and activation of undesired endonucleolytic activity at DSBs, which do not require endonucleolytic processing by Artemis. The Artemis:DNA PK complex could be involved in the repair of DSBs, which carry modified ends and are refractory to repair by otherwise lesion specific enzymes because of the presence of an inhibitory lesion in the opposite strand. J. Cell. Biochem. 100: 1346โ1351, 2007. ยฉ 2007 WileyโLiss, Inc.