
<ArticleTitle>Checkpoint activation in response to double-strand breaks requires the <prot>Mre11</prot>/<prot>Rad50</prot>/<prot>Xrs2</prot> complex.</ArticleTitle>
<AbstractText>Studies of human Nijmegen breakage syndrome (NBS) cells have led to the proposal that the <prot>Mre11</prot>/<prot>Rad50</prot>/ <prot>NBS1</prot> complex, which is involved in the repair of DNA double-strand breaks (DSBs), might also function in activating the DNA damage checkpoint pathways after DSBs occur. We have studied the role of the homologous budding yeast complex, <prot>Mre11</prot>/<prot>Rad50</prot>/<prot>Xrs2</prot>, in checkpoint activation in response to DSB-inducing agents. Here we show that this complex is required for phosphorylation and activation of the <prot>Rad53</prot> and <prot>Chk1</prot> checkpoint kinases specifically in response to DSBs. Consistent with defective <prot>Rad53</prot> activation, we observed defective cell-cycle delays after induction of DSBs in the absence of <prot>Mre11</prot>. Furthermore, after gamma-irradiation phosphorylation of <prot>Rad9</prot>, which is an early event in checkpoint activation, is also dependent on <prot>Mre11</prot>. All three components of the <prot>Mre11</prot>/<prot>Rad50</prot>/<prot>Xrs2</prot> complex are required for activation of <prot>Rad53</prot>, however, the <prot>Ku80</prot>, <prot>Rad51</prot> or <prot>Rad52</prot> proteins, which are also involved in DSB repair, are not. Thus, the integrity of the <prot>Mre11</prot>/<prot>Rad50</prot>/<prot>Xrs2</prot> complex is specifically required for checkpoint activation after the formation of DSBs.</AbstractText>
