Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map.
Defining the functional relationships between proteins is critical for understanding virtually all aspects of cell biology. Large-scale identification of protein complexes has provided one important step towards this goal; however, even knowledge of the stoichiometry, affinity and lifetime of every protein-protein interaction would not reveal the functional relationships between and within such complexes. Genetic interactions can provide functional information that is largely invisible to protein-protein interaction data sets. Here we present an epistatic miniarray profile (E-MAP) consisting of quantitative pairwise measurements of the genetic interactions between 743 Saccharomyces cerevisiae genes involved in various aspects of chromosome biology (including DNA replication/repair, chromatid segregation and transcriptional regulation). This E-MAP reveals that physical interactions fall into two well-represented classes distinguished by whether or not the individual proteins act coherently to carry out a common function. Thus, genetic interaction data make it possible to dissect functionally multi-protein complexes, including Mediator, and to organize distinct protein complexes into pathways. In one pathway defined here, we show that Rtt109 is the founding member of a novel class of histone acetyltransferases responsible for Asf1-dependent acetylation of histone H3 on lysine 56. This modification, in turn, enables a ubiquitin ligase complex containing the cullin Rtt101 to ensure genomic integrity during DNA replication.
Collins
Sean R
SR
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.
Miller
Kyle M
KM
Maas
Nancy L
NL
Roguev
Assen
A
Fillingham
Jeffrey
J
Chu
Clement S
CS
Schuldiner
Maya
M
Gebbia
Marinella
M
Recht
Judith
J
Shales
Michael
M
Ding
Huiming
H
Xu
Hong
H
Han
Junhong
J
Ingvarsdottir
Kristin
K
Cheng
Benjamin
B
Andrews
Brenda
B
Boone
Charles
C
Berger
Shelley L
SL
Hieter
Phil
P
Zhang
Zhiguo
Z
Brown
Grant W
GW
Ingles
C James
CJ
Emili
Andrew
A
Allis
C David
CD
Toczyski
David P
DP
Weissman
Jonathan S
JS
Greenblatt
Jack F
JF
Krogan
Nevan J
NJ
D000107:Acetylation; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D004843:Epistasis, Genetic; D006657:Histones / Q000378:metabolism; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012372:ROC Curve; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
D006657:Histones; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins