PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 2Citation - Scopus: 2Identification of Novel Arsenic Resistance Genes in Yeast(Wiley, 2022) Işık, Esin; Balkan, Çiğdem; Karl, Vivien; Karakaya, Hüseyin Çağlar; Hua, Sansan; Rauch, Sebastien; Tamás, Markus J; Koç, AhmetArsenic is a toxic metalloid that affects human health by causing numerous diseases and by being used in the treatment of acute promyelocytic leukemia. Saccharomyces cerevisiae (budding yeast) has been extensively utilized to elucidate the molecular mechanisms underlying arsenic toxicity and resistance in eukaryotes. In this study, we applied a genomic DNA overexpression strategy to identify yeast genes that provide arsenic resistance in wild-type and arsenic-sensitive S. cerevisiae cells. In addition to known arsenic-related genes, our genetic screen revealed novel genes, including PHO86, VBA3, UGP1, and TUL1, whose overexpression conferred resistance. To gain insights into possible resistance mechanisms, we addressed the contribution of these genes to cell growth, intracellular arsenic, and protein aggregation during arsenate exposure. Overexpression of PHO86 resulted in higher cellular arsenic levels but no additional effect on protein aggregation, indicating that these cells efficiently protect their intracellular environment. VBA3 overexpression caused resistance despite higher intracellular arsenic and protein aggregation levels. Overexpression of UGP1 led to lower intracellular arsenic and protein aggregation levels while TUL1 overexpression had no impact on intracellular arsenic or protein aggregation levels. Thus, the identified genes appear to confer arsenic resistance through distinct mechanisms but the molecular details remain to be elucidated.Article Citation - WoS: 9Citation - Scopus: 10Characterization of Long Living Yeast Deletion Mutants That Lack Mitochondrial Metabolism Genes Dss1, Ppa2 and Afg3(Elsevier, 2019) Muid, Khandaker Ashfaqul; Kimyon, Önder; Reza, Shahadat Hasan; Karakaya, Hüseyin Çağlar; Koç, AhmetMolecular mechanisms of aging and longevity are still mostly unknown. Mitochondria play central roles in cellular metabolism and aging. In this study, we identified three deletion mutants of mitochondrial metabolism genes (ppa2 Delta, dss1 Delta, and afg3 Delta) that live longer than wild-type cells. These long-lived cells harbored significantly decreased amount of mitochondria] DNA (mtDNA) and reactive oxygen species (ROS). Compared to the serpentine nature of wild-type mitochondria, a different dynamics and distribution pattern of mitochondria were observed in the mutants. Both young and old long-lived cells produced relatively low but adequate levels of ATP for cellular activities. The status of the retrograde signaling was checked by expression of CIT2 gene and found activated in long-lived mutants. The mutant cells were also profiled for their gene expression patterns, and genes that were differentially regulated were determined. All long-lived cells comprised similar pleiotropic phenotype regarding mitochondrial dynamics and functions. Thus, this study suggests that DSS1, PPA2, and AFG3 genes modulate the lifespan by altering the mitochondrial morphology and functions.Article Citation - WoS: 219Citation - Scopus: 242The Importance of Boron in Biological Systems(Urban und Fischer Verlag GmbH und Co. KG, 2018) Uluışık, İrem; Karakaya, Hüseyin Çağlar; Koç, AhmetBoron is an essential element for plants and probably essential for human and animal health. Boron has a broad range of physiological effects on biological systems at low concentrations, whereas it is toxic to at high concentrations. Eventhough there are many studies on boron's biological effects and toxicity, more information is needed to understand the mechanisms of its action. The aim of the current work is to review boron's function, transport and toxicity in different biological systems.Article Citation - WoS: 5Citation - Scopus: 4Characterization of a Cdna From Beta Maritima That Confers Nickel Tolerance in Yeast(Elsevier Ltd., 2014) Bozdağ, Gönensin Ozan; Kaya, Alaattin; Koç, Ahmet; Noll, Gundula A.; Prüfer, Dirk; Karakaya, Hüseyin ÇağlarNickel is an essential micronutrient due to its involvement in many enzymatic reactions as a cofactor. However, excess of this element is toxic to biological systems. Here, we constructed a cDNA library from Beta maritima and screened it in the yeast system to identify genes that confer resistance to toxic levels of nickel. A cDNA clone (NIC6), which encodes for a putative membrane protein with unknown function, was found to help yeast cells to tolerate toxic levels of nickel. A GFP fused form of Nic6 protein was localized to multivesicular structures in tobacco epidermal cells. Thus, our results suggest a possible role of Nic6 in nickel and intracellular ion homeostasis.Article Citation - WoS: 33Citation - Scopus: 40Characterization of Two Genes Encoding Metal Tolerance Proteins From Beta Vulgaris Subspecies Maritima That Confers Manganese Tolerance in Yeast(Springer Verlag, 2013) Erbaşol, Işıl; Bozdağ, Gönensin Ozan; Koç, Ahmet; Pedas, Pia; Karakaya, Hüseyin ÇağlarManganese (Mn2+) is an essential micronutrient in plants. However increased Mn2+ levels are toxic to plant cells. Metal tolerance proteins (MTPs), member of cation diffusion facilitator protein (CDF) family, have important roles in metal homeostatis in different plant species and catalyse efflux of excess metal ions. In this study, we identified and characterized two MTP genes from Beta vulgaris spp. maritima (B. v. ssp. maritima). Overexpression of these two genes provided Mn tolerance in yeast cells. Sequence analyses displayed BmMTP10 and BmMTP11as members of the Mn-CDF family. Functional analyses of these proteins indicated that they are specific to Mn2+ with a role in reducing excess cellular Mn2+ levels when expressed in yeast. GFP-fusion constructs of both proteins localized to the Golgi apparatus as a punctuated pattern. Finally, Q-RT-PCR results showed that BmMTP10 expression was induced threefold in response to the excess Mn2+ treatment. On the other hand BmMTP11 expression was not affected in response to excess Mn2+ levels. Thus, our results suggest that the BmMTP10 and BmMTP11 proteins from B. v. ssp. maritima have non-redundant functions in terms of Mn2+ detoxification with a similar in planta localization and function as the Arabidopsis Mn-CDF homolog AtMTP11 and this conservation shows the evolutionary importance of these vesicular proteins in heavy metal homeostatis among plant species.Article Citation - WoS: 12Citation - Scopus: 14Roles of Atr1 Paralogs Ymr279c and Yor378w in Boron Stress Tolerance(Elsevier Ltd., 2011) Bozdağ, Gönensin Ozan; Uluışık, İrem; Gülcüler, Gülce Sıla; Karakaya, Hüseyin Çağlar; Koç, AhmetBoron is a necessary nutrient for plants and animals, however excess of it causes toxicity. Previously, Atr1 and Arabidopsis Bor1 homolog were identified as the boron efflux pump in yeast, which lower the cytosolic boron concentration and help cells to survive in the presence of toxic amount of boron. In this study, we analyzed ATR1 paralogs, YMR279c and YOR378w, to understand whether they participate in boron stress tolerance in yeast. Even though these genes share homology with ATR1, neither their deletion rendered cells boron sensitive nor their expression was significantly upregulated by boron treatment. However, expression of YMR279, but not YOR378w, from the constitutive GAPDH promoter on a high copy plasmid provided remarkable boron resistance by decreasing intracellular boron levels. Thus our results suggest the presence of a third boron exporter, YMR279c, which functions similar to ATR1 and provides boron resistance in yeast.Article Citation - WoS: 48Citation - Scopus: 52Boron Stress Activates the General Amino Acid Control Mechanism and Inhibits Protein Synthesis(Public Library of Science, 2011) Uluışık, İrem; Kaya, Alaattin; Fomenko, Dmitri E.; Karakaya, Hüseyin Çağlar; Carlson, Bradley A.; Gladyshev, Vadim N.; Koç, AhmetBoron is an essential micronutrient for plants, and it is beneficial for animals. However, at high concentrations boron is toxic to cells although the mechanism of this toxicity is not known. Atr1 has recently been identified as a boron efflux pump whose expression is upregulated in response to boron treatment. Here, we found that the expression of ATR1 is associated with expression of genes involved in amino acid biosynthesis. These mechanisms are strictly controlled by the transcription factor Gcn4 in response to boron treatment. Further analyses have shown that boron impaired protein synthesis by promoting phosphorylation of eIF2α in a Gcn2 kinase dependent manner. The uncharged tRNA binding domain (HisRS) of Gcn2 is necessary for the phosphorylation of eIF2α in the presence of boron. We postulate that boron exerts its toxic effect through activation of the general amino acid control system and inhibition of protein synthesis. Since the general amino acid control pathway is conserved among eukaryotes, this mechanism of boron toxicity may be of general importance.Article Citation - WoS: 20Citation - Scopus: 20Genome-Wide Identification of Genes That Play a Role in Boron Stress Response in Yeast(Elsevier Ltd., 2011) Uluışık, İrem; Kaya, Alaattin; Ünlü, Ercan Selçuk; Avşar, Kadir; Karakaya, Hüseyin Çağlar; Yalçın, Talat; Koç, AhmetBoron is an essential micronutrient for plants and it is either necessary or beneficial for animals. Studies identified only few genes related to boron metabolism thus far and details of how boron is imported into cells and used in cell metabolism are largely unknown. In order to identify genes that play roles in boron metabolism, we screened the entire set of yeast haploid deletion mutants and identified 6 mutants that were resistant to toxic levels of boron, and 21 mutants that were highly sensitive to boron treatment. Furthermore, we performed a proteomic approach to identify additional proteins that are significantly up-regulated by boron treatment. Our results revealed many genes and pathways related to boron stress response and suggest a possible link between boron toxicity and translational control.Article Citation - WoS: 55Citation - Scopus: 64Identification of a Novel System for Boron Transport: Atr1 Is a Main Boron Exporter in Yeast(American Society for Microbiology, 2009) Kaya, Alaattin; Karakaya, Hüseyin Çağlar; Fomenko, Dmitri E.; Gladyshev, Vadim N.; Koç, AhmetBoron is a micronutrient in plants and animals, but its specific roles in cellular processes are not known. To understand boron transport and functions, we screened a yeast genomic DNA library for genes that confer resistance to the element in Saccharomyces cerevisiae. Thirty boron-resistant transformants were isolated, and they all contained the ATR1 (YML116w) gene. Atr1 is a multidrug resistance transport protein belonging to the major facilitator superfamily. C-terminal green fluorescent protein-tagged Atr1 localized to the cell membrane and vacuole, and ATR1 gene expression was upregulated by boron and several stress conditions. We found that atr1△ mutants were highly sensitive to boron treatment, whereas cells overexpressing ATR1 were boron resistant. In addition, atr1△ cells accumulated boron, whereas ATR1-overexpressing cells had low intracellular levels of the element. Furthermore, atr1△ cells showed stronger boron-dependent phenotypes than mutants deficient in genes previously reported to be implicated in boron metabolism. ATR1 is widely distributed in bacteria, archaea, and lower eukaryotes. Our data suggest that Atr1 functions as a boron efflux pump and is required for boron tolerance.