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1 Biological Engineering Division and Center for Environmental Health Sciences and 2 Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA
Requests for reprints: Leona D. Samson, Biological Engineering Division and Center for Environmental Health Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139. Phone: (617) 258-7813; Fax: (617) 253-8099. E-mail: lsamson{at}mit.edu
We have generated a genomic phenotyping database identifying hundreds of Saccharomyces cerevisiae genes important for viable cellular recovery after mutagen exposure. Systematic phenotyping of 1615 gene deletion strains produced distinctive signatures for each of four mutagens. Integration of the phenotyping database with mutagen-induced transcriptional profiling data demonstrated that being transcriptionally responsive to a mutagen does not predict whether or not a gene contributes to recovery from exposure to that mutagen. Computational integration of the database with 4025 interacting proteins, comprising the yeast interactome, identified several multiprotein networks important for damage recovery. Some networks were associated with DNA metabolism and cell cycle control functions, but most were associated with unexpected functions such as cytoskeleton remodeling, chromatin remodeling, protein, RNA, and lipid metabolism. Hence, a plethora of responses other than the DNA damage response is important for recovery. These network mapping results demonstrate how systematic phenotypic assays may be linked directly to underlying molecular mechanisms.
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