Network responses to DNA damaging agents.
Global transcriptional profiling and large scale phenotypic studies have shown that eukaryotic cells mount a robust and complex response to damage. Further, systems biology approaches have employed powerful analytical methods to integrate global data sets with regulatory sequences, protein-DNA and protein-protein interactions, which have led to the identification of large networked responses to damage. A number of groups have shown that damage responsive networks embrace groups of highly connected genes and proteins and have illustrated that multiple interconnected cellular pathways respond to damage and moreover, dictate viability post damage. This review highlights some of the global studies that examine cellular responses to damage, and proposes that we should be moving from pathways to networks, in order to gain better insight into cellular defense mechanisms.
Biological Engineering Division and Center for Environmental Health Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Thomas J
TJ
Begley
Leona D
LD
Samson
D000818:Animals; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry; D006801:Humans; D008741:Methyl Methanesulfonate; D008954:Models, Biological; D008957:Models, Genetic; D009153:Mutagens; D010641:Phenotype; D011485:Protein Binding; D049490:Systems Biology; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D009153:Mutagens; D004247:DNA; D008741:Methyl Methanesulfonate