Peer-Reviewed Journal Details
Mandatory Fields
Grenon, M,Gilbert, C,Lowndes, NF
2001
September
Nature Cell Biology
Checkpoint activation in response to double-strand breaks requires the Mre11/Rad50/Xrs2 complex
Published
()
Optional Fields
DNA-DAMAGE CHECKPOINT LYMPHOBLASTOID CELL-LINES BUDDING YEAST MEC1-DEPENDENT PHOSPHORYLATION ATAXIA-TELANGIECTASIA PROTEIN COMPLEX CYCLE REPAIR RAD53 INTERACTS
3
844
847
Studies of human Nijmegen breakage syndrome (NBS) cells have led to the proposal that the Mre11/Rad50/NBS1 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(1,2). We have studied the role of the homologous budding yeast complex, Mre11/Rad50/Xrs2, in checkpoint activation in response to DSB-inducing agents. Here we show that this complex is required for phosphorylation and activation of the Rad53 and Chk1 checkpoint kinases specifically in response to DSBs. Consistent with defective Rad53 activation, we observed defective cell-cycle delays after induction of DSBs in the absence of Mrell. Furthermore, after gamma -irradiation phosphorylation of Rad9, which is an early event in checkpoint activation, is also dependent on Mre11. All three components of the Mre11/Rad50/Xrs2 complex are required for activation of Rad53, however, the Ku80, Rad51 or Rad52 proteins, which are also involved in DSB repair, are not. Thus, the integrity of the Mre11/Rad50/Xrs2 complex is specifically required for checkpoint activation after the formation of DSBs.
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