Functional Organization of the S. cerevisiae Phosphorylation Network

Abstract

Summary Reversible protein phosphorylation is a signaling mechanism involved in all cellular processes. To create a systems view of the signaling apparatus in budding yeast, we generated an E-MAP (epistatic miniarray profile) comprised of 100,000 pair-wise, quantitative genetic interactions, including virtually all protein kinases and phosphatases and key cellular regulators. Quantitative genetic interaction mapping reveals factors working in compensatory pathways (negative genetic interactions; e.g. synthetic lethality) or those operating in linear pathways (positive genetic interactions; e.g. suppression). Within kinases, phosphatases, and their substrates, we found an enrichment of positive genetic interactions. To develop a global view of the signaling apparatus, we isolated “triplet genetic motifs” and assembled these into a higher-order map. The resulting network view provides new insights into signaling pathway regulation, and revealed a link between the cell cycle kinase, Cak1, the Fus3 MAP kinase, and a pathway that regulates chromatin integrity during transcription by RNA polymerase II.

Replisome Function During Replicative Stress Is Modulated by Histone H3 Lysine 56 Acetylation Through Ctf4

“…As previously suggested by genetic screens (Pan et al 2006;Collins et al 2007;Fiedler et al 2009;Costanzo et al 2010), we observed that RRM3 disruption strongly affects the growth of asf1D cells (see below). To characterize the genetic interaction between ASF1 and RRM3, one allele of ASF1 was deleted in an RRM3/rrm3D diploid.…”

“…These results, showing a specific enrichment of Mms22 at forks in the absence of RRM3, are consistent with our genetic observations obtained with the Ctf4 mutants. They reinforce our conclusion that the interaction between Ctf4 and Mms22 is regulated during replicative damage and is crucial in dealing with replicative stress.Replisome destabilization allows cells lacking a functional H3K56ac pathway to survive under replicative stressTo better understand the role of H3K56ac at forks, we extended our analysis to another crucial component of the Fiedler et al 2009;Haber et al 2013), it is possible that the replicative function of MRC1 could also be deleterious in the presence of DNA damage, when H3K56ac is compromised. To test this possibility, because mrc1D is synthetic lethal with rrm3D (Naylor et al 2009), we first examined the effects of the MRC1 deletion in asf1D cells subjected to replicative stress.…”

Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance

“…Ser/Thr/Tyr phosphorylations are ubiquitous in eukaryotes (2,50). These types of protein phosphorylations dominate eukaryotic signaling and regulation.…”

Phosphorylation of Right Open Reading Frame 2 (Rio2) Protein Kinase by Polo-like Kinase 1 Regulates Mitotic Progression

“…Casein kinase I isoform Hrr25 not only regulates the maturation of 40 S ribosomal subunits (23), but also participates in the transcriptional response to DNA damage (24). It has been reported that Rio2 interacted with many proteins involved in ribosome biogenesis in yeast as well as proteins involved in cell proliferation (25)(26)(27)(28)(29), indicating that Rio2 may have dual functions in ribosome biogenesis and cell proliferation. However, the role of Rio2 in cell proliferation has not been addressed.…”