Rewiring of genetic networks in response to DNA damage

Science. 2010 Dec 3;330(6009):1385-9. doi: 10.1126/science.1195618.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Chromatin
  • DNA, Fungal
  • Histones
  • Htz1 protein, S cerevisiae
  • Mutagens
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Methyl Methanesulfonate
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • SLT2 protein, S cerevisiae
  • PPH3 protein, S cerevisiae
  • Phosphoprotein Phosphatases