The frequency of genomic mutations is much lower in embryonic stem cells (ES cells) than in somatic cells, but the mechanisms that contribute to genome stability in ES cells remain largely unknown. Xiong et al. now find that the zinc-finger protein Sall4, which is known to be important for the maintenance of stemness, is required for activating the ATM-dependent cellular responses to DNA double-stranded breaks (DSBs) in mouse ES cells. Autophosphorylation of ATM at Ser1987, a marker for ATM activation, was greatly reduced in Sall4−/− cells following the induction of DSBs. Moreover, phosphorylation of ATM target proteins was decreased and levels of DNA damage were increased, indicating that Sall4 is required for activation of the ATM-dependent repair pathway. The authors show that Sall4 is recruited to sites of DNA DSBs, through interactions with the chromatin remodelling factor Baf60a (a member of the SWI/SNF complex), where they stabilize the Mre11-Rad50-Nbs1 (MRN) complex that links DSBs to ATM signalling.