25 genome-wide responses to dna-damaging agents arm

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Genome-Wide Responses to DNA-Damaging Agents Rebecca C. Fry, 1 Thomas J. Begley, 2 and Leona D. Samson 1 1 Biological Engineering Division and Center for Environmental Health Sciences, Massachusetts Institute of T echnology , Cambridge, Massachusetts 02139; email: [email protected], [email protected] 2 Department of Biomedical Sciences and Gen ∗ NY ∗ Sis Center for Excellence in Cancer Genomics, University at Albany-SUNY , Rensselaer, New York 12144; email: tbegley@albany .edu Annu. Rev. Microbiol. 2005. 59:357–77 First published online as a Review in Advance on June 14, 2005 The Annual Review of Microbiology is online at micro.annualreviews.org doi: 10.1146/ annurev.micro.59.031805.133658 Copyright c 2005 by Annual Reviews. All rights reserved 0066-4227/05/1013- 0357$20.00 Key Words DNA repair, systems biology, transcription profiling, networks, phenotypic profiling Abstract Genome-wid e studi es of mRNA regulati on and phenotyp ic responses have shown that eukaryotic cells mount a robust and mul- tifaceted response upon exposure to DNA-damaging agents. The integration of theses studies over frameworks provided by protein- protein interactions, protein-DNA interactions, and subcellular lo- calization information have led to the identification of networked responses to damage. Taken together, these studies illustrate that cellular protection from DNA and other macromolecular damage involves an intricate network of proteins involved in many different cellular functions, some of them expected (e.g., DNA repair and cell cycle checkpoints) but many of them unexpected (e.g., protein traf- ficking and degradation). This review highlights many of the studies that detail genome-wide responses to DNA-damaging agents and examines how these datasets have been used to build a systems view of cellular responses to damage. 357 A n n u . R e v . M i c r o b i o l . 2 0 0 5 . 5 9 : 3 5 7 3 7 7 . D o w n l o a d e d f r o m a r j o u r n a l s . a n n u a l r e v i e w s . o r g b y H A R V A R D U N I V E R S I T Y o n 0 2 / 0 3 / 0 6 . F o r p e r s o n a l u s e o n l y .

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