FIGURE 5: Novel genetic interactors unveil a functional link between Rnr3 and mitochondria. (A) The SGA database lists 130 genetic interactors of RNR3 (Tables S2) [32]. Functional Specification (FunSpec) analysis [39] unveils enrichment of several GO Biological Process terms (Tables S3). (B) Ten fold serial dilutions of the indicated strains were spotted onto YPD or YPG and incubated at the indicated temperatures. (C) WT and rnr3Δ cells transformed with a RNR3-, rnr3-C428A-, or an empty LEU2 vector plasmid were spotted onto SD-LEU, SG-LEU, or SG-LEU plus EthBr (0.5 µg/ml) and incubated at the indicated temperatures. (D) Model: Mec1 and carbon source dependent regulation of Rnr1 and Rnr3 facilitates fermentative and respiratory growth. (i) Abundant glucose induces Rnr1 in preparation for rapid proliferation and a greater demand for dNTPs. (ii) Glucose depletion or non fermentable carbon sources down regulate Rnr1 as a means to attenuate dNTP production in preparation for slowed growth under respiratory conditions. (iii) Mec1 mediates the respiratory carbon source dependent induction of Rnr3 independently of its DDR network. (iv) Mec1 also facilitates the glucose dependent down regulation of Rnr3 via a mechanism yet to be elucidated.

32. Costanzo M et al. (2016). A global genetic interaction network maps a wiring diagram of cellular function. Science 353(6306): aaf1420–aaf1420. doi: 10.1126/science.aaf1420

39. Robinson MD, Grigull J, Mohammad N, and Hughes TR (2002). FunSpec: a web-based cluster interpreter for yeast. BMC Bioinformatics 3: 35. doi: 10.1186/1471-2105-3-35