A Systems Approach to Mapping DNA Damage Response Pathways

Workman, C.T. and Mak, H.C. and McCuine, S. and et al, . (2006) A Systems Approach to Mapping DNA Damage Response Pathways. Science, 312 (5776). pp. 1054-1059.

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Failure of cells to respond to DNA damage is a primary event associated with mutagenesis and environmental toxicity. To map the transcriptional network controlling the damage response, we measured genomewide binding locations for 30 damage-related transcription factors (TFs) after exposure of yeast to methyl-methanesulfonate (MMS). The resulting 5272 TF-target interactions revealed extensive changes in the pattern of promoter binding and identified damage-specific binding motifs. As systematic functional validation, we identified interactions for which the target changed expression in wild-type cells in response to MMS but was nonresponsive in cells lacking the TF. Validated interactions were assembled into causal pathway models that provide global hypotheses of how signaling, transcription, and phenotype are integrated after damage

Item Type: Article
Uncontrolled Keywords: DNA damage, Environmental toxicity, Genes, Phenotypic sensitivity
Author Affiliation: University of California San Diego, La Jolla, CA 92093
Subjects: Crop Improvement > Genetics/Genomics
Divisions: General
Depositing User: Ms Ishrath Durafsha
Date Deposited: 13 Nov 2014 04:30
Last Modified: 13 Nov 2014 04:30
Official URL: http://dx.doi.org/10.1126/science.1122088
URI: http://eprints.icrisat.ac.in/id/eprint/13513

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