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In this review, we have summarized the information from a study on FKBP12 (FK506 binding protein 12 kDa) with a view to understand its drug-free, physiological roles in transcription of ribosomal protein gene in Saccharomyces cerevisiae. FKBP12 with peptidyl-prolylisomerase (PPIase) activity is widely conserved among many eukaryotes. FKBP12 is a primary target for the two structurally related drugs

The RecA-family recombinase Rad51 is the central player in homologous recombination (HR), the faithful pathway for repairing DNA double-strand breaks (DSBs) during both mitosis and meiosis. The behavior of Rad51 protein in vivo is fine-tuned via posttranslational modifications conducted by multiple protein kinases in response to cell cycle cues and DNA lesions. Unrepaired DSBs and ssDNA also activate

Since its description in S. cerevisiae, the Regulation of Ace2 and Morphogenesis (RAM) pathway has been studied for nearly 20 years in multiple model and pathogenic fungi. In pathogenic fungi, the RAM pathway carries out many functions through mechanisms that remain to be defined in detail. Recently, we reported that Cbk1-mediated phosphorylation of the transcription factor Ace2 functions to repress

DNA replication checkpoint is a cell signaling pathway that is activated in response to perturbed replication. Although it is crucial for maintaining genomic integrity and cell survival, the exact mechanism of the checkpoint signaling remains to be understood. Emerging evidence has shown that RecQ helicases, a large family of helicases that are conserved from bacteria to yeasts and humans, contribute

Polyphosphates (polyP) are polymers of inorganic phosphates joined by high-energy bonds to form long chains. These chains are present in all forms of life but were once disregarded as ‘molecular fossils’. PolyP has gained attention in recent years following new links to diverse biological roles ranging from energy storage to cell signaling. PolyP research in humans and other higher eukaryotes is limited

During amino acid limitation, the protein kinase Gcn2 phosphorylates the α subunit of eIF2, thereby regulating mRNA translation. In yeast Saccharomyces cerevisiae and mammals, eIF2α phosphorylation regulates translation of related transcription factors Gcn4 and Atf4 through upstream open reading frames (uORFs) to activate transcription genome wide. However, mammals encode three more eIF2α kinases activated

Cohesin is essential for sister chromatid cohesion, which ensures equal segregation of the chromatids to daughter cells. However, the molecular mechanism by which cohesin mediates this function is elusive. Scc3, one of the four core subunits of cohesin, is vital to cohesin activity. However, the mechanism by which Scc3 contributes to the activity and identity of its functional domains is not fully

The AAA-ATPase p97/Cdc48 is one of the most abundant proteins in eukaryotes, and owing to its multiple functions, is considered the swiss army knife of cells. Recent findings demonstrate that p97/Cdc48 and its cofactor p47/Shp1 control the heavy metal stress response by active, signal-triggered disassembly of a multisubunit ubiquitin ligase. Here we review this pathway and describe recently achieved

Fumonisins are a group of mycotoxins produced by maize pathogen Fusarium verticillioides that pose health concerns to humans and animals. Yet we still lack a clear understanding of the mechanism of fumonisins regulation during pathogenesis. The heterotrimeric G protein complex, which consists of canonical subunits and various regulators of G-protein signaling (RGS) proteins, plays an important role

Polarized growth is required in eukaryotic cells for processes such as cell division, morphogenesis and motility, which involve conserved and interconnected signalling pathways controlling cell cycle progression, cytoskeleton reorganization and secretory pathway functioning. While many of the factors involved in polarized growth are known, it is not yet clear how they are coordinated both spatially

Morphological transitions in Candida species are key factors in facilitating invasion and adapting to environmental changes. N-acetylglucosamine (GlcNAc) is a monosaccharide signalling molecule that can regulate morphological transitions in Candida albicans and Candida tropicalis. Interestingly, although the uptake and metabolic pathways of GlcNAc and GlcNAc-mediated white-to-opaque cell switching

DNA polymerase IV (pol IV) is expressed at increased levels in Escherichia coli cells that suffer DNA damage. In a recent live-cell single-molecule fluorescence microscopy study, we demonstrated that the formation of pol IV foci is strongly recB-dependent in cells treated with the DNA break-inducing antibiotic ciprofloxacin. The results of that study support a model in which pol IV acts to extend D-loop

Yeast Apn2 is an AP endonuclease and DNA 3′-diesterase that belongs to the Exo III family with homology to the E. coli exonuclease III, Schizosaccharomyces pombe eth1, and human AP endonucleases APEX1 and APEX2. In the absence of Apn1, the major AP endonuclease in yeast, Apn2 can cleave the DNA backbone at an AP lesion initiating the base excision repair pathway. To study the role and relative contribution

Protein phosphorylation catalyzed by protein kinases is the major regulatory mechanism that controls many cellular processes. The regulatory mechanism of one protein kinase in different signals is distinguished, probably inducing multiple phenotypes. The Saccharomyces cerevisiae Snf1 protein kinase, a member of the AMP‑activated protein kinase family, plays important roles in the response to nutrition

Under thermal stress, different protein quality control (PQC) strategies are activated to maintain an intact proteome, which may vary from one model system to another. Hence thermo-sensitive proteins that lose their active conformation might be refolded with the aid of chaperones or removed by the ubiquitin–proteasome system or the process of autophagy. We have recently developed thermo-sensitive reporters

The cloning of plasmids can be time-consuming or expensive. Yet, cloning is a prerequisite for many standard experiments for the functional analysis of genes, including the generation of deletion mutants and the localization of gene products. Here, we provide Golden Gate vectors for fast and easy cloning of gene fusion as well as gene deletion vectors applicable to diverse fungi. In Golden Gate cloning

Cell aging is the result of deteriorating competence in maintaining cellular homeostasis and quality control. Certain cell types are able to rejuvenate through asymmetric cell division by excluding aging factors, including damaged cellular compartments and extrachromosomal rDNA circles, from entering the daughter cell. Recent findings from the budding yeast S. cerevisiae have shown that gametogenesis

Gene transcription is a complex biological process that involves a set of factors, enzymes and nucleotides. Ssu72 plays a crucial role in every step of gene transcription. RNA polymerase II (RNAPII) occupies an important position in the synthesis of mRNAs. The largest subunit of RNAPII, Rpb1, harbors its C-terminal domain (CTD), which participates in the initiation, elongation and termination of transcription

The coordinated action of DNA polymerases and DNA helicases is essential at genomic sites that are hard to replicate. Among these are sites that harbour G-quadruplex DNA structures (G4). G4s are stable alternative DNA structures, which have been implicated to be involved in important cellular processes like the regulation of gene expression or telomere maintenance. G4 structures were shown to hinder

The kinetochore is a mega-dalton protein assembly that forms within centromeric regions of chromosomes and directs their segregation during cell division. Here we review cell cycle-mediated phosphorylation events at the kinetochore, with a focus on the budding yeast Saccharomyces cerevisiae and the insight gained from forced associations of kinases and phosphatases. The point centromeres found in the

Phenotypic and genetic heterogeneities are conserved features of prokaryotic populations. During periods of stress, this programmed diversity increases the likelihood that variants within the population will survive the adverse conditions, allowing for proliferation. Phenotypic heterogeneity can have a mutational or indeed a non-mutational basis as observed in bet-hedging strategies adopted by antibiotic-tolerant

Yeast cells adapt to alkaline conditions by activating the Rim101 alkali-responsive pathway. Rim21 acts as a sensor in the Rim101 pathway and detects extracellular alkalization. Interestingly, Rim21 is also known to be activated by alterations involving the lipid asymmetry of the plasma membrane. In this study, we briefly summarize the mechanism of activation and the signal transduction cascade of

Yeast is one of the best-understood biological systems for genetic research. Over the last 40 years, geneticists have striven to search for homologues of tumor suppressors in yeast to simplify cancer research. The star tumor suppressor p21, downstream target of p53, is one of the primary factors on the START point through negatively regulating CycD/E-CDK, the yeast counterpart Cln3-Cdk1. Not like yeast

Controlling chromatin state constitutes a major regulatory step in gene expression regulation across eukaryotes. While global cellular features or processes are naturally impacted by chromatin state alterations, little is known about how chromatin regulatory genes interact in networks to dictate downstream phenotypes. Using the activity of the canonical galactose network in yeast as a model, here,

The rates and patterns by which cells acquire mutations profoundly shape their evolutionary trajectories and phenotypic potential. Conventional models maintain that mutations are acquired independently of one another over many successive generations. Yet, recent evidence suggests that cells can also experience mutagenic processes that drive rapid genome evolution. One such process manifests as punctuated

Telomeres are specialized nucleoprotein complexes that protect the ends of eukaryotic chromosomes and distinguish them from broken DNA ends. Disruption of telomere protection may cause aging-associated pathologies and cancer. Here, we examined what makes telomere protection durable and resistant to perturbations using a budding yeast model organism. The protein Rap1 binds the telomeric repeats, negatively

Cells divide with appropriate frequency by coupling division to growth—that is, cells divide only when they have grown sufficiently large. This process is poorly understood, but has been studied using cell size mutants. In principle, mutations affecting cell size could affect the mean size (“set-point” mutants), or they could affect the variability of sizes (“homeostasis” mutants). In practice, almost

Phyto-pathogenic fungi can cause huge damage to crop production. During millions of years of coexistence, fungi have evolved diverse life-style to obtain nutrients from the host and to colonize upon them. They deploy various proteinaceous as well as non-proteinaceous secreted molecules commonly referred as effectors to sabotage host machinery during the infection process. The effectors are important

This perspective aims to discuss the potential physiological roles and regulation mechanisms of the recently identified Candida albicans Wss1 protease important in DNA−protein crosslink (DPC) tolerance and repair. DPC is a bulky DNA lesion that blocks essential DNA transactions; thus, it poses a significant threat to genome integrity if left unrepaired. Discoveries of Wss1 in Saccharomyces cerevisiae

Yeast and cancer cells are metabolically similar as they use fermentation of glucose as a primary means of generating energy. Reliance on glucose fermentation makes both of these cell types highly sensitive to the toxic glucose analog, 2-deoxyglucose. Here we review the cellular and metabolic pathways that play a role in 2-deoxyglucose sensitivity and discuss how the modifications to these pathways

Global methods for assaying translation have greatly improved our understanding of the protein-coding capacity of the genome. In particular, it is now possible to perform genome-wide and condition-specific identification of translation initiation sites through modified ribosome profiling methods that selectively capture initiating ribosomes. Here we discuss our recent study applying such an approach

β-tubulin, a component of microtubules, is involved in a wide variety of roles in cell shape, motility, intracellular trafficking and regulating intracellular metabolism. It has been an important fungicide target to control plant pathogen, for example, Fusarium. However, the regulation of fungicide sensitivity by β-tubulin-interacting proteins is still unclear. Here, ASK1 was identified as a β-tubulin

Multiple exogenous and endogenous genotoxic agents threaten the integrity of the genome, but one major source of spontaneous DNA damage is the formation of unscheduled DNA–RNA hybrids. These can be genetically detected by their ability to induce recombination. The origin of spontaneous hybrids has been mainly attributed to the nascent RNA formed co-transcriptionally in cis invading its own DNA template

PIF1 family helicases are evolutionarily conserved among prokaryotes and eukaryotes. These enzymes function to support genome integrity by participating in multiple DNA transactions that can be broadly grouped into DNA replication, DNA repair, and telomere maintenance roles. However, the levels of PIF1 activity in cells must be carefully controlled, as Pif1 over-expression in Saccharomyces cerevisiae

Protein phosphorylation is an essential regulatory mechanism that controls most cellular processes, integrating a variety of environmental signals to drive cellular growth. Isr1 is a negative regulator of the hexosamine biosynthesis pathway (HBP), which produces UDP-GlcNAc, an essential carbohydrate that is the building block of N-glycosylation, GPI anchors and chitin. Isr1 was recently shown to be

Translating ribosomes slow down or completely stall when they encounter obstacles on mRNAs. Such events can lead to ribosomes colliding with each other and forming complexes of two (disome), three (trisome) or more ribosomes. While these events can activate surveillance pathways, it has been unclear if collisions are common on endogenous mRNAs and whether they are usually detected by these cellular

The notion that there is a one–one mapping from genotype to phenotype was overturned a long time ago. Along with genotype and environment, ‘non-genetic changes’ orchestrated by altered RNA and protein molecules also guide the development of phenotype. The idea that there is a route through which changes in phenotype can lead to changes in genotype impinges on several phenomena of molecular, developmental

Gene silencing by the SIR (Silent Information Region) family of proteins in S. cerevisiae has been extensively studied and has served as a founding paradigm for our general understanding of gene repression and its links to histone deacetylation and chromatin structure. In recent years, our understanding of other mechanisms of gene repression in S.cerevisiae was significantly advanced. In this review

Replication-coupled (RC) nucleosome assembly is an essential process in eukaryotic cells to maintain chromatin structure during DNA replication. The deposition of newly-synthesized H3/H4 histones during DNA replication is facilitated by specialized histone chaperones. CAF-1 is an important histone chaperone complex and its main subunit, Cac1p, contains a PIP and WHD domain for interaction with PCNA

The amino acid biosynthetic pathway of invasive pathogenic fungi has been studied as a potential antifungal drug target. Studies of the disruption of genes involved in amino acid biosynthesis have demonstrated the importance of this pathway in the virulence of Cryptococcus neoformans. Here, we identified the MET5 (CNL05500) and MET10 (CNG03990) genes in this pathway, both encoding sulfite reductase

Mapping of effective protein domains is a demanding stride to disclose the functional relationship between regulatory complexes. Domain analysis of protein interactions is requisite for understanding the pleiotropic responses of the respective partners. Cti6 is a multifunctional regulator for which we could show recruitment of co-repressors Sin3, Cyc8 and Tup1. However, the responsible core domain

Living cells have developed a set of complex signaling responses, which allow them to withstand different environmental challenges. Signaling pathways enable the cell to monitor external and internal states and to articulate the appropriate physiological responses. Cellular signal transmission requires the dynamic formation of spatiotemporal controlled molecular interactions. One of the most important

The disease-associated nuclease–helicase DNA2 has been implicated in DNA end-resection during DNA double-strand break repair, Okazaki fragment processing, and the recovery of stalled DNA replication forks (RFs). Its role in Okazaki fragment processing has been proposed to explain why DNA2 is indispensable for cell survival across organisms. Unexpectedly, we found that DNA2 has an essential role in

RNA/DNA hybrids are processed by RNases H1 and H2, while single ribonucleoside-monophosphates (rNMPs) embedded in genomic DNA are removed by the error-free, RNase H2-dependent ribonucleotide excision repair (RER) pathway. In the absence of RER, however, topoisomerase 1 (Top1) can cleave single genomic rNMPs in a mutagenic manner. In RNase H2-deficient mice, the accumulation of genomic rNMPs above a

Bacteria and other prokaryotes evolve primarily through rapid changes in their gene content by quickly losing and gaining genes whenever an ecological opportunity emerges. As gene loss and horizontal gene transfer (HGT) appear to be the most common events across the prokaryotic tree of life, we need to think beyond gradual sequence evolution if we wish to understand the microbial world. Especially

The human fungal pathogen Candida albicans maintains pathogenic and commensal states primarily through cell wall functions. The echinocandin antifungal drug caspofungin inhibits cell wall synthesis and is widely used in treating disseminated candidiasis. Signaling pathways are critical in coordinating the adaptive response to cell wall damage (CWD). C. albicans executes a robust transcriptional program

Posttranscriptional modifications of anticodon loops contribute to the decoding efficiency of tRNAs by supporting codon recognition and loop stability. Consistently, strong synthetic growth defects are observed in yeast strains simultaneously lacking distinct anticodon loop modifications. These phenotypes are accompanied by translational inefficiency of certain mRNAs and disturbed protein homeostasis

Fusarium graminearum produces trichothecene mycotoxins in infected grains and axenic liquid culture. A proposed regulatory model of trichothecene biosynthesis was examined in relation to nitrogen utilization. First, we showed that an important factor for the stimulation of trichothecene biosynthesis was not the occurrence of agmatine as a specific inducer molecule, but rather continuous acidification

Because metabolism is a complex balanced process involving multiple enzymes, understanding how organisms compensate for transient or permanent metabolic imbalance is a challenging task that can be more easily achieved in simpler unicellular organisms. The metabolic balance results not only from the combination of individual enzymatic properties, regulation of enzyme abundance, but also from the architecture

The opportunistic fungal pathogen Candida albicans is able to switch among several morphological phenotypes in response to environmental changes. White–opaque transition is a typical phenotypic switching system involved in the regulation of pathogenesis and sexual reproduction in C. albicans. Under regular laboratory culture conditions, to undergo white-to-opaque switching, cells must first undergo

Halotolerant species are adapted to dealing continually with hyperosmotic environments, having evolved strategies that are uncommon in other organisms. The HOG pathway is the master system that regulates the cellular adaptation under these conditions; nevertheless, apart from the importance of Debaryomyces hansenii as an organism representative of the halotolerant class, its HOG1 pathway has been poorly

The original version of this article unfortunately contained a mistake.

Transcriptional reinduction memory is a phenomenon whereby cells “remember” their transcriptional response to a previous stimulus such that subsequent encounters with the same stimulus can result in altered gene expression kinetics. Chromatin structure is thought to play a role in certain transcriptional memory mechanisms, leading to questions as to whether and how memory can be actively maintained

In vivo transposon mutagenesis, coupled with deep sequencing, enables large-scale genome-wide mutant screens for genes essential in different growth conditions. We analyzed six large-scale studies performed on haploid strains of three yeast species (Saccharomyces cerevisiae, Schizosaccaromyces pombe, and Candida albicans), each mutagenized with two of three different heterologous transposons (AcDs

Homologous recombination is essential for the maintenance of genome integrity but must be strictly controlled to avoid dangerous outcomes that produce the opposite effect, genomic instability. During unperturbed chromosome replication, recombination is globally inhibited at ongoing DNA replication forks, which helps to prevent deleterious genomic rearrangements. This inhibition is carried out by Srs2

Boi1 and Boi2 are paralogous proteins essential for bud formation in budding yeast. So far, the domains that target Boi1/Boi2 to the polarity sites and function in bud formation are not well understood. Here, we report that a coiled-coil domain of Boi2 cooperates with the adjacent PH domain to confer Boi2’s bud-cortex localization and major function in cell growth. The PH domain portion of the PH-CC

During mitosis, the identical sister chromatids of each chromosome must attach through their kinetochores to microtubules emanating from opposite spindle poles. This process, referred to as chromosome biorientation, is essential for equal partitioning of the genetic information to the two daughter cells. Defects in chromosome biorientation can give rise to aneuploidy, a hallmark of cancer and genetic

Certain replication-blocking lesions can escape DNA repair and must be bypassed to prevent fork collapse and cell death. Budding yeast DNA-damage tolerance consists of translesion DNA synthesis (TLS) and template switch. TLS utilizes specialized DNA polymerases to insert nucleotides opposite the damage site, followed by extension, allowing continual replication in the presence of lesions on the template

The endoplasmic reticulum (ER) stress potentially activates the unfolded protein response (UPR) and ER-associated protein degradation (ERAD) as quality-control mechanisms. During ERAD process, the ERAD adaptor protein Ubx2 serves as a bridging factor and transports the misfolded proteins from the ER to the cytosol for subsequent ubiquitylation and proteasomal degradation. Cadmium (Cd) is a toxic metal