Gamma-H2AX formation by activated ATM kinase is one of the few earliest responses to a double-strand DNA break. Nibrin (NBS1) becomes phosphorylated upon ATM activation. However, the presence of the MRN (MRE11-RAD50-NBS1) complex at the DNA damage site is required for proper recruitment and activation of ATM. Thus, transport of the MRN-complex to the nuclear double strand breaks occurs independent of ATM. At the damage site, the activated ATM further phosphorylates H2AX and NBS1. Phosphorylated H2AX then recruits additional MRN complex using contacts to NBS1, which amplifies the activation of ATM. Increases in the level of active ATM results in increased phosphorylation of target proteins, facilitating recruitment of repair proteins to DSBs. Whether NBS1 forms a complex with gamma H2AX first and then get phosphorylated by ATM, or phospho NBS1 is recruited to the DSB by complex formation with gamma-H2AX is unclear.