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.
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Sourav
S
Bandyopadhyay
Monika
M
Mehta
Dwight
D
Kuo
Min-Kyung
MK
Sung
Ryan
R
Chuang
Eric J
EJ
Jaehnig
Bernd
B
Bodenmiller
Katherine
K
Licon
Wilbert
W
Copeland
Michael
M
Shales
Dorothea
D
Fiedler
Janusz
J
Dutkowski
Aude
A
Guénolé
Haico
H
van Attikum
Kevan M
KM
Shokat
Richard D
RD
Kolodner
Won-Ki
WK
Huh
Ruedi
R
Aebersold
Michael-Christopher
MC
Keogh
Nevan J
NJ
Krogan
Trey
T
Ideker
D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004271:DNA, Fungal / Q000235:genetics; D004843:Epistasis, Genetic; D053263:Gene Regulatory Networks; D005800:Genes, Fungal; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D004271:DNA, Fungal; D006657:Histones; C493530:Htz1 protein, S cerevisiae; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D008741:Methyl Methanesulfonate; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae; C502440:PPH3 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases