Our group has developed and exhaustively screened genetic interactions (GIs) at a genome-wide scale under standard growth conditions [1]. The Synthetic Genetic Array (SGA) methodology has also been used to explore how genetic interactions change in response to DNA damage and other stress conditions (e.g. [2, 3]), but a systematic exploration of the condition-sensitivity of genetic interactions has not been undertaken. We are building a conditional GI reference dataset, using high density single and double mutant arrays grown on agar plate. We aim at probing cellular responses to a panel of chemical-induced stress targeted at essential functions such as DNA and membrane integrity, transcription, translation and protein turnover, nutrient quality and sensing. As a proof of principle, we crossed ~200 condition-sensitive mutant query strains with a mini-array of 1200 highly informative mutant bait strains and performed a SGA analysis in six different growth conditions. Surprisingly, we observed genes that previously failed to be characterized by SGA under standard growth conditions displaying conditional GIs for specific functions, revealing their purpose in stress-induced cells. For example, the gene URM1 encoding an ubiquitin-like protein shared GIs with genes annotated for chromatin remodeling and signal transduction, both functions being suggested for urmylation in cells [4, 5]. Moreover, genes implicated in condition stress-response demonstrate GIs enrich for expected and unexpected functions, the latest represent new functions or functional switch under specific stress conditions. For instance, the target of rapamycin (TOR) kinase (TOR1, TOR2) and regulators shared GIs enrich for ribosome biogenesis (10-8), chromatin remodeling (10-6), chromosome segregation (10-5) and DNA replication (10-5). Chromosome missegregation and chromatin remodeling were described as a target in rapamycin treated yeast cells [6, 7]. The regulation of DNA replication by rapamycin-induced stress is novel and requires further validation. We, therefore, assemble data supporting a role of TOR activity in DNA replication under rapamycin growth.
[1] Costanzo et al. 2016 Science, under revision; [2]Bandyopadhyay et al. 2010 Science 300, 1385-9; [3] Martin et al. 2015 Nat Genet. 47, 410-4; [4] Haarer et al. 2013 G3 3, 553-61; [5] Goehring et al.2003 MBOC 14, 4329-4; [6] Worley et al. 2016 G3 6, 463-74; [7] Choi et al. 2000 Cur biol. 10, 861-4.