MRE11/RAD50/NBS1: complex activities.
The MRE11/RAD50/NBS1 complex (Mre11 complex) is a central player in most aspects of the cellular response to DNA double-strand breaks, including homologous recombination, non-homologous end joining, telomere maintenance and DNA damage checkpoint activation. Several of these findings are explained by the unusual enzymatic activities and macromolecular structure of the Mre11 complex. The Mre11 complex possesses an ATP-stimulated nuclease to process heterogeneous DNA ends and long coiled-coil tails to link DNA ends and/or sister chromatids. However, the mechanistic role of the Mre11 complex in checkpoint activation has been unclear until recently. New data suggest that the Mre11 complex can directly activate the ATM checkpoint kinase at DNA breaks. These findings, together with newly determined functional interactions, identify the Mre11 complex as an architectural and mechanistic keystone of cellular response events emerging from DNA breaks.
Assenmacher
Nora
N
Gene Center, University of Munich, Feodor-Lynen-Str. 25, 81377 Munich, Germany.
Hopfner
Karl-Peter
KP
D017766:Acid Anhydride Hydrolases; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019457:Chromosome Breakage; D004265:DNA Helicases / Q000502:physiology; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D003851:Deoxyribonucleases / Q000502:physiology; D006801:Humans; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D003851:Deoxyribonucleases; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D004265:DNA Helicases; D045643:DNA Repair Enzymes