The cellular response to DNA double-strand breaks: defining the sensors and mediators.
The induction of DNA double-strand breaks (DSBs) culminates in the activation of cell cycle checkpoint responses and DNA repair machinery. The mechanism of DSB detection remains unclear although many candidate sensor proteins have been identified through cytologic, biochemical and genetic studies. In light of recent advances in our understanding of the cellular response to DSBs, we have proposed criteria for defining sensor proteins. We discuss the possible role of the Mre11 complex as a primary damage sensor and the complex relationship between DNA damage sensors, transducers and mediators.
Petrini
John H J
JH
Molecular Biology Program, Memorial Sloan Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, New York, NY 10021, USA. petrinij@mskcc.org
Stracker
Travis H
TH
D048868:Adaptor Proteins, Signal Transducing; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D000076228:MRE11 Homologue Protein; D008958:Models, Molecular; D008968:Molecular Conformation; D009687:Nuclear Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C413163:MDC1 protein, human; C121766:MRE11 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; D000076228:MRE11 Homologue Protein