A Systems Approach to Mapping DNA Damage Response Pathways

Overview

Journal Science

Specialty Science

Date 2006 May 20

PMID 16709784

Citations 128

Authors

Christopher T Workman

H Craig Mak

Scott McCuine

Jean-Bosco Tagne

Maya Agarwal

Owen Ozier

Thomas J Begley

Leona D Samson

Trey Ideker

Affiliations

Soon will be listed here.

Abstract

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.

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