Checkpoint activation in response to double-strand breaks requires the Mre11/Rad50/Xrs2 complex.

Abstract	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. 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 Mre11. 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.
Authors	M Grenon, C Gilbert, N F Lowndes
Journal	Nature cell biology (Nat Cell Biol) Vol. 3 Issue 9 Pg. 844-7 (Sep 2001) ISSN: 1465-7392 [Print] England
PMID	11533665 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Cell Cycle Proteins DNA-Binding Proteins Fungal Proteins MRE11 protein, human RAD50 protein, S cerevisiae Saccharomyces cerevisiae Proteins XRS2 protein, S cerevisiae rad9 protein Endodeoxyribonucleases Exodeoxyribonucleases MRE11 Homologue Protein MRE11 protein, S cerevisiae
Topics	Cell Cycle (genetics, physiology, radiation effects) Cell Cycle Proteins (metabolism) Cell Line DNA Damage DNA Repair DNA-Binding Proteins (metabolism) Endodeoxyribonucleases Exodeoxyribonucleases Fungal Proteins (metabolism) G1 Phase G2 Phase Gamma Rays Humans MRE11 Homologue Protein Phosphorylation Saccharomyces cerevisiae (cytology, genetics) Saccharomyces cerevisiae Proteins

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