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Rewiring of genetic networks in response to DNA damage.

Although cellular behaviors are dynamic, the networks that govern these behaviors have been mapped primarily as static snapshots. Using an approach called differential epistasis mapping, we have discovered widespread changes in genetic interaction among yeast kinases, phosphatases, and transcription factors as the cell responds to DNA damage. Differential interactions uncover many gene functions that go undetected in static conditions. They are very effective at identifying DNA repair pathways, highlighting new damage-dependent roles for the Slt2 kinase, Pph3 phosphatase, and histone variant Htz1. The data also reveal that protein complexes are generally stable in response to perturbation, but the functional relations between these complexes are substantially reorganized. Differential networks chart a new type of genetic landscape that is invaluable for mapping cellular responses to stimuli.

Pubmed ID: 21127252

Authors

  • Bandyopadhyay S
  • Mehta M
  • Kuo D
  • Sung MK
  • Chuang R
  • Jaehnig EJ
  • Bodenmiller B
  • Licon K
  • Copeland W
  • Shales M
  • Fiedler D
  • Dutkowski J
  • Guénolé A
  • van Attikum H
  • Shokat KM
  • Kolodner RD
  • Huh WK
  • Aebersold R
  • Keogh MC
  • Krogan NJ
  • Ideker T

Journal

Science (New York, N.Y.)

Publication Data

December 3, 2010

Associated Grants

  • Agency: NCI NIH HHS, Id: P30CA013330
  • Agency: NIGMS NIH HHS, Id: P50 GM081879
  • Agency: NIEHS NIH HHS, Id: R01 ES014811
  • Agency: NIEHS NIH HHS, Id: R01 ES014811-01A1
  • Agency: NIEHS NIH HHS, Id: R01 ES014811-02
  • Agency: NIEHS NIH HHS, Id: R01 ES014811-02S1
  • Agency: NIEHS NIH HHS, Id: R01 ES014811-03
  • Agency: NIEHS NIH HHS, Id: R01 ES014811-04
  • Agency: NIEHS NIH HHS, Id: R01 ES014811-05
  • Agency: NIEHS NIH HHS, Id: R01 ES014811-05S1
  • Agency: NIEHS NIH HHS, Id: R01 ES014811-06
  • Agency: NIGMS NIH HHS, Id: R01 GM026017
  • Agency: NIGMS NIH HHS, Id: R01 GM084279
  • Agency: NIGMS NIH HHS, Id: R01 GM084279-01A1
  • Agency: NIGMS NIH HHS, Id: R01 GM084279-02
  • Agency: NIGMS NIH HHS, Id: R01 GM084279-02S1
  • Agency: NIGMS NIH HHS, Id: R01 GM084279-03
  • Agency: NIGMS NIH HHS, Id: R01 GM084279-04
  • Agency: NIGMS NIH HHS, Id: R01 GM084448
  • Agency: NIEHS NIH HHS, Id: R01-ES14811
  • Agency: NIGMS NIH HHS, Id: R01-GM084279
  • Agency: NIGMS NIH HHS, Id: R37 GM026017
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Chromatin
  • DNA Damage
  • DNA Repair
  • DNA, Fungal
  • Epistasis, Genetic
  • Gene Regulatory Networks
  • Genes, Fungal
  • Histones
  • Methyl Methanesulfonate
  • Mitogen-Activated Protein Kinases
  • Mutagens
  • Mutation
  • Phosphoprotein Phosphatases
  • Protein Interaction Mapping
  • Protein-Serine-Threonine Kinases
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Signal Transduction
  • Transcription Factors