TY - JOUR
T1 - Dissection of DNA Damage Responses Using Multiconditional Genetic Interaction Maps
AU - Guénolé, Aude
AU - Srivas, Rohith
AU - Vreeken, Kees
AU - Wang, Ze Zhong
AU - Wang, Shuyi
AU - Krogan, Nevan J.
AU - Ideker, Trey
AU - van Attikum, Haico
N1 - Funding Information:
The authors thank G. Hannum and N. de Wind for helpful discussions; J. Shen, M. Tijsterman, and H. Vrieling for critical reading of the manuscript; H. Braberg and A. Roguev for assistance with the genetic interaction screens; M. Lisby, K.J. Myung, S. Ben-Aroya, and P. Hieter for providing reagents. R.S., T.I., and N.J.K., who is a Searle Scholar and a Keck Young Investigator, were generously supported by grants from the U.S. National Institutes of Health (ES014811 and GM084279 to R.S. and T.I.; GM084448, GM084279, GM081879, and GM098101 to N.J.K.). H.v.A. was supported by grants from the Netherlands Organization for Scientific Research (NWO-VIDI) and a CDA grant from Human Frontiers Science Program (HFSP).
PY - 2013/1/24
Y1 - 2013/1/24
N2 - To protect the genome, cells have evolved a diverse set of pathways designed to sense, signal, and repair multiple types of DNA damage. To assess the degree of coordination and crosstalk among these pathways, we systematically mapped changes in the cell's genetic network across a panel of different DNA-damaging agents, resulting in ∼1,800,000 differential measurements. Each agent was associated with a distinct interaction pattern, which, unlike single-mutant phenotypes or gene expression data, has high statistical power to pinpoint the specific repair mechanisms at work. The agent-specific networks revealed roles for the histone acetyltranferase Rtt109 in the mutagenic bypass of DNA lesions and the neddylation machinery in cell-cycle regulation and genome stability, while the network induced by multiple agents implicates Irc21, an uncharacterized protein, in checkpoint control and DNA repair. Our multiconditional genetic interaction map provides a unique resource that identifies agent-specific and general DNA damage response pathways.
AB - To protect the genome, cells have evolved a diverse set of pathways designed to sense, signal, and repair multiple types of DNA damage. To assess the degree of coordination and crosstalk among these pathways, we systematically mapped changes in the cell's genetic network across a panel of different DNA-damaging agents, resulting in ∼1,800,000 differential measurements. Each agent was associated with a distinct interaction pattern, which, unlike single-mutant phenotypes or gene expression data, has high statistical power to pinpoint the specific repair mechanisms at work. The agent-specific networks revealed roles for the histone acetyltranferase Rtt109 in the mutagenic bypass of DNA lesions and the neddylation machinery in cell-cycle regulation and genome stability, while the network induced by multiple agents implicates Irc21, an uncharacterized protein, in checkpoint control and DNA repair. Our multiconditional genetic interaction map provides a unique resource that identifies agent-specific and general DNA damage response pathways.
UR - https://www.scopus.com/pages/publications/84872821321
U2 - 10.1016/j.molcel.2012.11.023
DO - 10.1016/j.molcel.2012.11.023
M3 - Article
C2 - 23273983
AN - SCOPUS:84872821321
SN - 1097-2765
VL - 49
SP - 346
EP - 358
JO - Molecular Cell
JF - Molecular Cell
IS - 2
ER -