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Ataxia telangectasia mutated (ATM) is required for the ea rly response to DNA damage agents such as ionizing radiation (IR) that induce DNA double strand breaks (DSBs).Cells deficient in ATM are extremely sensitive to IR.It has been shown that ionizing radiation (IR) induces immediate phosphorylation of Ser1981 of ATM, leading to catalytic activation of the protein.We recently isolated a novel BRCA1-associated protein, BAAT1 (BRCA1-associated protein required for ATM activation-1), by yeast two-hybrid screening and found that BAAT1 also binds to ATM, localizes to DSBs and is required for Ser1981 phosphorylation ofATM.siRNA-mediated stable or transient reduction of BAAT1 resulted in decreased phosphorylation of both Ser1981 of ATM and Thr68 of Chk2.Treatment of BAAT1-depleted cells with okadaic acid greatly restored phosphorylation ofATM Ser1981, suggesting that BAAT1 is involved in regulation ofATM phosphatase.PP2A-mediated dephosphorylation of ATM was partially blocked by purified BAAT1 in vitro.Significantly, acute loss of BAAT1 resulted in increased p53, leading to apoptosis.These results demonstrate that DNA damage-induced ATM activation requires a coordinated assembly ofBRCA1, BAAT1 and ATM.