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. (C) 2004 Elsevier B.V. All rights reserved.