@article{5d71fc856fcb4e6eb7717b2bb6e6576a,
title = "Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map",
abstract = "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.",
author = "Collins, {Sean R.} and Miller, {Kyle M.} and Maas, {Nancy L.} and Assen Roguev and Jeffrey Fillingham and Chu, {Clement S.} and Maya Schuldiner and Marinella Gebbia and Judith Recht and Michael Shales and Huiming Ding and Hong Xu and Junhong Han and Kristin Ingvarsdottir and Benjamin Cheng and Brenda Andrews and Charles Boone and Berger, {Shelley L.} and Phil Hieter and Zhiguo Zhang and Brown, {Grant W.} and Ingles, {C. James} and Andrew Emili and Allis, {C. David} and Toczyski, {David P.} and Weissman, {Jonathan S.} and Greenblatt, {Jack F.} and Krogan, {Nevan J.}",
note = "Funding Information: Acknowledgements We are grateful to K. Tipton and M. Bassik for critically reading the manuscript, S. Gasser, B. Frey and Vincent Cheung for discussion, and G. Narlikar for reagents. We thank N. Datta, T. Punna, N. Thompson, M. Ballantine, N. Gabovic, A. Wind, K. Chin, Y. Xue, A. Chan, Y. Xue, T. Chan, M. Xan, M. Lim, H. Dalgleish, K. Vachon, L. Le, C. Sun, Z. Hassam, J. Rilestone and K. Takhar for technical assistance. We also thank S. Jackson, Z. Zhang, Vanessa Cheung, F. Winston, J. Erkmann and P. Kaufman for communicating results before publication. This research was supported by grants from Genome Canada and the Ontario Genomics Institute (J.F.G., A.E., C.B. and B.A.), the NIH (D.P.T.), the Howard Hughes Medical Institute (J.S.W.) and the Canadian Institute of Health Research (N.J.K., C.J.I. and G.W.B.). S.R.C. was funded by a fellowship from the Burroughs Wellcome Fund. N.J.K. is a Sandler Family Fellow.",
year = "2007",
month = apr,
day = "12",
doi = "10.1038/nature05649",
language = "English (US)",
volume = "446",
pages = "806--810",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7137",
}