#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
preLekára.sk / Odborné časopisy / PLOS Genetics / 2013 - 10

Yeast Tdh3 (Glyceraldehyde 3-Phosphate Dehydrogenase) Is a Sir2-Interacting Factor That Regulates Transcriptional Silencing and rDNA Recombination

English version České info

Sir2 is an NAD+-dependent histone deacetylase required to mediate transcriptional silencing and suppress rDNA recombination in budding yeast. We previously identified Tdh3, a glyceraldehyde 3-phosphate dehydrogenase (GAPDH), as a high expression suppressor of the lethality caused by Sir2 overexpression in yeast cells. Here we show that Tdh3 interacts with Sir2, localizes to silent chromatin in a Sir2-dependent manner, and promotes normal silencing at the telomere and rDNA. Characterization of specific TDH3 alleles suggests that Tdh3's influence on silencing requires nuclear localization but does not correlate with its catalytic activity. Interestingly, a genetic assay suggests that Tdh3, an NAD+-binding protein, influences nuclear NAD+ levels; we speculate that Tdh3 links nuclear Sir2 with NAD+ from the cytoplasm.

Vyšlo v časopise: Yeast Tdh3 (Glyceraldehyde 3-Phosphate Dehydrogenase) Is a Sir2-Interacting Factor That Regulates Transcriptional Silencing and rDNA Recombination. PLoS Genet 9(10): e32767. doi:10.1371/journal.pgen.1003871
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003871

Souhrn

Sir2 is an NAD+-dependent histone deacetylase required to mediate transcriptional silencing and suppress rDNA recombination in budding yeast. We previously identified Tdh3, a glyceraldehyde 3-phosphate dehydrogenase (GAPDH), as a high expression suppressor of the lethality caused by Sir2 overexpression in yeast cells. Here we show that Tdh3 interacts with Sir2, localizes to silent chromatin in a Sir2-dependent manner, and promotes normal silencing at the telomere and rDNA. Characterization of specific TDH3 alleles suggests that Tdh3's influence on silencing requires nuclear localization but does not correlate with its catalytic activity. Interestingly, a genetic assay suggests that Tdh3, an NAD+-binding protein, influences nuclear NAD+ levels; we speculate that Tdh3 links nuclear Sir2 with NAD+ from the cytoplasm.

Zdroje

1. ImaiS-i, GuarenteL (2010) Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases. Trends in Pharmacological Sciences 31 : 212–220.

2. LuS-P, LinS-J (2010) Regulation of yeast sirtuins by NAD+ metabolism and calorie restriction. Biochim Biophys Acta 1804 : 1567–1575.

3. HaberJE (2012) Mating-type genes and MAT switching in Saccharomyces cerevisiae. Genetics 191 : 33–64.

4. YoungTJ, KirchmaierAL (2012) Cell cycle regulation of silent chromatin formation. Biochim Biophys Acta 1819 : 303–312.

5. GottliebS, EspositoRE (1989) A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA. Cell 56 : 771–776.

6. SmithJS, BoekeJD (1997) An unusual form of transcriptional silencing in yeast ribosomal DNA. Genes Dev 11 : 241–254.

7. BrykM, BanerjeeM, MurphyM, KnudsenK, GarfinkelD, et al. (1997) Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast. Genes Dev 11 : 255–269.

8. QiuX, BrownKV, MoranY, ChenD (2010) Sirtuin regulation in calorie restriction. Biochim Biophys Acta 1804 : 1576–1583.

9. KatadaS, ImhofA, Sassone-CorsiP (2012) Connecting threads: epigenetics and metabolism. Cell 148 : 24–28.

10. SandmeierJJ, CelicI, BoekeJD, SmithJS (2002) Telomeric and rDNA silencing in Saccharomyces cerevisiae are dependent on a nuclear NAD(+) salvage pathway. Genetics 160 : 877–889.

11. BelenkyP, RacetteFG, BoganKL, McClureJM, SmithJS, et al. (2007) Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell 129 : 473–484.

12. MatecicM, StuartS, HolmesSG (2002) SIR2-induced inviability is suppressed by histone H4 overexpression. Genetics 162 : 973–976.

13. McAlisterL, HollandMJ (1985) Differential Expression of three Yeast Glyceraldehyde-3-phosphate Dehydrogenase Genes. J Biol Chem 260 : 15019–15027.

14. McAlisterL, HollandMJ (1985) Isolation and characterization of yeast strains carrying mutations in the glyceraldehyde-3-phosphate dehydrogenase genes. J Biol Chem 260 : 15013–15018.

15. BoucherieH, BatailleN, FitchI, PerrotM, TuiteM (1995) Differential synthesis of glyceraldehyde-3-phosphate dehydrogenase polypeptides in stressed yeast cells. FEMS Microbiol Lett 125 : 127–133.

16. ValadiH, ValadiA, AnsellR, GustafssonL, AdlerL, et al. (2004) NADH-reductive stress in Saccharomyces cerevisiae induces the expression of the minor isoform of glyceraldehyde-3-phosphate dehydrogenase (TDH1). Curr Gen 45 : 90–95.

17. RoyN, RungeKW (2000) Two paralogs involved in transcriptional silencing that antagonistically control yeast life span. Curr Biol 10 : 111–114.

18. RossmannMP, LuoW, TsaponinaO, ChabesA, StillmanB (2011) A common telomeric gene silencing assay is affected by nucleotide metabolism. Mol Cell 42 : 127–136.

19. TakahashiY-H, SchulzeJM, JacksonJ, HentrichT, SeidelC, et al. (2011) Dot1 and Histone H3K79 Methylation in Natural Telomeric and HM Silencing. Mol Cell 42 : 118–126.

20. Vega-PalasMA, Martin-FigueroaE, FlorencioFJ (2000) Telomeric silencing of a natural subtelomeric gene. Mol Gen Genet 263 : 287–291.

21. TisdaleE, KellyC, ArtalejoC (2004) Glyceraldehyde-3-phosphate dehydrogenase interacts with Rab2 and plays an essential role in endoplasmic reticulum to Golgi transport exclusive of its glycolytic activity. J Biol Chem 279 : 54046–54052.

22. ParkJ, HanD, KimK, KangY, KimY (2009) O-GlcNAcylation disrupts glyceraldehyde-3-phosphate dehydrogenase homo-tetramer formation and mediates its nuclear translocation. Biochim Biophys Acta 1794 : 254–262.

23. SiroverMA (2011) On the functional diversity of glyceraldehyde-3-phosphate dehydrogenase: biochemical mechanisms and regulatory control. Biochim Biophys Acta 1810 : 741–751.

24. KimJ-W, DangCV (2005) Multifaceted roles of glycolytic enzymes. Trends Bioc Sci 30 : 142–150.

25. HowsonR, HuhW-K, GhaemmaghamiS, FalvoJV, BowerK, et al. (2005) Construction, verification and experimental use of two epitope-tagged collections of budding yeast strains. Comp Funct Genom 6 : 2–16.

26. StutzR, RosbashM (1994) A functional interaction between Rev and yeast pre-mRNA is related to splicing complex formation. EMBO J 13 : 4096–4104.

27. FritzeCC, GreenMR (1996) HIV Rev uses a conserved cellular protein export pathway for the nucleocytoplasmic transport of viral RNAs. Curr Biol 6 : 848–854.

28. HickmanM, McCulloughK, WoikeA, Raducha-GraceL, RozarioT, et al. (2007) Isolation and characterization of conditional alleles of the yeast SIR2 gene. J Mol Biol 367 : 1246–1257.

29. GavinAC, BoscheM, KrauseR, GrandiP, MarziochM, et al. (2002) Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415 : 141–147.

30. Koch-NolteF, FischerS, HaagF, ZieglerM (2011) Compartmentation of NAD+-dependent signalling. FEBS Lett 585 : 1651–1656.

31. AndersonR, Latorre-EstevesM, NevesA, LavuS, MedvedikO, et al. (2003) Yeast life-span extension by calorie restriction is independent of NAD fluctuation. Science 302 : 2124–2126.

32. OoiSL, PanX, PeyserBD, YeP, MeluhPB, et al. (2006) Global synthetic-lethality analysis and yeast functional profiling. Trends Genet 22 : 56–63.

33. PanX, YeP, YuanDS, WangX, BaderJS, et al. (2006) A DNA Integrity Network in the Yeast Saccharomyces cerevisiae. Cell 124 : 1069–1081.

34. AndersonR, BittermanK, WoodJ, MedvedikO, CohenH, et al. (2002) Manipulation of a Nuclear NAD+ Salvage Pathway Delays Aging without Altering Steady-state NAD+ Levels. J Biol Chem 277 : 18881–18890.

35. SmithJ, BrachmannC, CelicI, KennaM, MuhammadS, et al. (2000) A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family. Proc Nat Acad Sci USA 97 : 6658–6663.

36. TristanC, ShahaniN, SedlakTW, SawaA (2011) The diverse functions of GAPDH: views from different subcellular compartments. Cell Signal 23 : 317–323.

37. GiotL, BaderJS, BrouwerC, ChaudhuriA, KuangB, et al. (2003) A protein interaction map of Drosophila melanogaster. Science 302 : 1727–1736.

38. KornbergMD, SenN, HaraMR, JuluriKR, NguyenJVK, et al. (2010) GAPDH mediates nitrosylation of nuclear proteins. Nat Cell Biol 12 : 1094–1100.

39. JooH-Y, WooSR, ShenY-N, YunMY, ShinH-J, et al. (2012) SIRT1 interacts with and protects glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from nuclear translocation: implications for cell survival after irradiation. Biochem Biophys Res Commun 424 : 681–686.

40. LiM, ValsakumarV, PooreyK, BekiranovS, SmithJS (2013) Genome-wide analysis of functional sirtuin chromatin targets in yeast. Genome Biology 14: R48.

41. RalserM, ZeidlerU, LehrachH, LorenzMC (2009) Interfering with Glycolysis Causes Sir2-Dependent Hyper-Recombination of Saccharomyces cerevisiae Plasmids. PLoS ONE 4: e5376.

42. RalserM (2012) Sirtuins as regulators of the yeast metabolic network. Front Pharmacol 3 : 1–15.

43. BorraMT, LangerMR, SlamaJT, DenuJM (2004) Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases. Biochemistry 43 : 9877–9887.

44. DenuJM (2007) Vitamins and aging: pathways to NAD+ synthesis. Cell 129 : 453–454.

45. LinSJ, DefossezPA, GuarenteL (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289 : 2126–8.

46. KaeberleinM, KirklandKT, FieldsS, KennedyBK (2004) Sir2-independent life span extension by calorie restriction in yeast. PLoS Biol 2: e296.

47. EvansC, BoganKL, SongP, BurantCF, KennedyRT, et al. (2010) NAD+ metabolite levels as a function of vitamins and calorie restriction: evidence for different mechanisms of longevity. BMC Chem Biol 10 : 2.

48. LinSJ, FordE, HaigisM, LisztG, GuarenteL (2004) Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev 18 : 12.

49. TsuchiyaM, DangN, KerrE, HuD, SteffenK, et al. (2006) Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeast. Aging Cell 5 : 505–514.

50. WachA, BrachatA, PohlmannR, PhilippsenP (1994) New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast 10 : 1793–1808.

51. GoldsteinA, McCuskerJ (1999) Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae. Yeast 15 : 1541–1553.

52. KnopM, SiegersK, PereiraG, ZachariaeW, WinsorB, et al. (1999) Epitope tagging of yeast genes using a PCR-based strategy: more tags and improved practical routines. Yeast 15 : 963–972.

53. StoriciF, LewisLK, ResnickMA (2001) In vivo site-directed mutagenesis using oligonucleotides. Nat Biotechnol 19 : 773–776.

54. HortonR, HuntH, HoS, PullenJ, PeaseL (1989) Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension. Gene 77 : 61–68.

55. GiaeverG, ChuAM, NiL, ConnellyC, RilesL, et al. (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418 : 387–391.

56. TongAH, EvangelistaM, ParsonsAB, XuH, BaderGD, et al. (2001) Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science 294 : 2364–2368.

57. JinQW, FuchsJ, LoidlJ (2000) Centromere clustering is a major determinant of yeast interphase nuclear organization. J Cell Sci 113(Pt 11): 1903–1912.

58. RockmillB (2009) Chromosome spreading and immunofluorescence methods in Saccharomyes cerevisiae. Methods Mol Biol 558 : 3–13.

59. MotwaniT, PoddarM, HolmesSG (2012) Sir3 and Epigenetic Inheritance of Silent Chromatin in Saccharomyces cerevisiae. Mol Cell Biol 32 : 2784–2793.

60. Martins-TaylorK, SharmaU, RozarioT, HolmesSG (2011) H2A.Z (Htz1) controls the cell-cycle-dependent establishment of transcriptional silencing at Saccharomyces cerevisiae telomeres. Genetics 187 : 89–104.

61. SukaN, SukaY, CarmenAA, WuJ, GrunsteinM (2001) Highly specific antibodies determine histone acetylation site usage in yeast heterochromatin and euchromatin. Mol Cell 8 : 473–479.

62. RudnerAD, HallBE, EllenbergerT, MoazedD (2005) A nonhistone protein-protein interaction required for assembly of the SIR complex and silent chromatin. Mol Cell Biol 25 : 4514–4528.

63. HsuSC, MoldayRS (1990) Glyceraldehyde-3-phosphate dehydrogenase is a major protein associated with the plasma membrane of retinal photoreceptor outer segments. J Biol Chem 265 : 13308–13313.

64. RalserM, WamelinkMM, KowaldA, GerischB, HeerenG, et al. (2007) Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress. J Biol 6 : 10.

65. KeoghM-C, MennellaTA, SawaC, BertheletS, KroganNJ, et al. (2006) The Saccharomyces cerevisiae histone H2A variant Htz1 is acetylated by NuA4. Genes Dev 20 : 660–665.

66. DarstRP, GarciaSN, KochMR, PillusL (2008) Slx5 Promotes Transcriptional Silencing and Is Required for Robust Growth in the Absence of Sir2. Mol Cell Biol 28 : 1361–1372.

67. RenauldH, AparicioO, ZierathP, BillingtonB, ChhablaniS, et al. (1993) Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and by SIR3 dosage. Genes Dev 7 : 1133–1145.

68. SusselL, VannierD, ShoreD (1993) Epigenetic switching of transcriptional states: cis -⁠ and trans-acting factors affecting establishment of silencing at the HMR locus in Saccharomyces cerevisiae. Mol Cell Biol 13 : 3919–3928.

69. JamesP, HalladayJ, CraigEA (1996) Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast. Genetics 144 : 1425–1436.

70. UetzP, GiotL, CagneyG, MansfieldTA, JudsonRS, et al. (2000) A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 403 : 623–627.

71. ChiMH, ShoreD (1996) SUM1-1, a dominant suppressor of SIR mutations in Saccharomyces cerevisiae, increases transcriptional silencing at telomeres and HM mating-type loci and decreases chromosome stability. Mol Cell Biol 16 : 4281–4294.

72. MatecicM, Martins-TaylorK, HickmanM, TannyJ, MoazedD, et al. (2006) New alleles of SIR2 define cell-cycle-specific silencing functions. Genetics 173 : 1939–1950.

Štítky
Genetika Reprodukčná medicína
Článek Defending Sperm Function
Článek How to Choose the Right Mate
Článek A Mutation in the Gene in Labrador Retrievers with Hereditary Nasal Parakeratosis (HNPK) Provides Insights into the Epigenetics of Keratinocyte Differentiation
Článek Conserved Translatome Remodeling in Nematode Species Executing a Shared Developmental Transition
Článek A Novel Actin mRNA Splice Variant Regulates ACTG1 Expression
Článek Tracking Proliferative History in Lymphocyte Development with Cre-Mediated Sister Chromatid Recombination
Článek Correlated Occurrence and Bypass of Frame-Shifting Insertion-Deletions (InDels) to Give Functional Proteins
Článek Chimeric Protein Complexes in Hybrid Species Generate Novel Phenotypes
Článek Loss of miR-10a Activates and Collaborates with Activated Wnt Signaling in Inducing Intestinal Neoplasia in Female Mice
Článek Both Rare and Copy Number Variants Are Prevalent in Agenesis of the Corpus Callosum but Not in Cerebellar Hypoplasia or Polymicrogyria
Článek Reverse PCA, a Systematic Approach for Identifying Genes Important for the Physical Interaction between Protein Pairs
Článek Partial Deletion of Chromosome 8 β-defensin Cluster Confers Sperm Dysfunction and Infertility in Male Mice
Článek Genome-Wide and Cell-Specific Epigenetic Analysis Challenges the Role of Polycomb in Spermatogenesis
Článek Coordinate Regulation of Mature Dopaminergic Axon Morphology by Macroautophagy and the PTEN Signaling Pathway
Článek Cooperation between RUNX1-ETO9a and Novel Transcriptional Partner KLF6 in Upregulation of in Acute Myeloid Leukemia
Článek Mobility of the Native Conjugative Plasmid pLS20 Is Regulated by Intercellular Signaling
Článek FliZ Is a Global Regulatory Protein Affecting the Expression of Flagellar and Virulence Genes in Individual Bacterial Cells
Článek Specific Tandem Repeats Are Sufficient for Paramutation-Induced Trans-Generational Silencing
Článek Condensin II Subunit dCAP-D3 Restricts Retrotransposon Mobilization in Somatic Cells
Článek Dominant Mutations in Identify the Mlh1-Pms1 Endonuclease Active Site and an Exonuclease 1-Independent Mismatch Repair Pathway
Článek The Insulator Homie Promotes Expression and Protects the Adjacent Gene from Repression by Polycomb Spreading
Článek Human Intellectual Disability Genes Form Conserved Functional Modules in
Článek Coordination of Cell Proliferation and Cell Fate Determination by CES-1 Snail
Článek ORFs in Drosophila Are Important to Organismal Fitness and Evolved Rapidly from Previously Non-coding Sequences
Článek Different Roles of Eukaryotic MutS and MutL Complexes in Repair of Small Insertion and Deletion Loops in Yeast
Článek The Spore Differentiation Pathway in the Enteric Pathogen
Článek Acceleration of the Glycolytic Flux by Steroid Receptor Coactivator-2 Is Essential for Endometrial Decidualization
Článek The Human Nuclear Poly(A)-Binding Protein Promotes RNA Hyperadenylation and Decay
Článek Genome Wide Analysis Reveals Zic3 Interaction with Distal Regulatory Elements of Stage Specific Developmental Genes in Zebrafish
Článek Xbp1 Directs Global Repression of Budding Yeast Transcription during the Transition to Quiescence and Is Important for the Longevity and Reversibility of the Quiescent State
Článek The Integrator Complex Subunit 6 (Ints6) Confines the Dorsal Organizer in Vertebrate Embryogenesis
Článek Incorporating Motif Analysis into Gene Co-expression Networks Reveals Novel Modular Expression Pattern and New Signaling Pathways
Článek The Bacterial Response Regulator ArcA Uses a Diverse Binding Site Architecture to Regulate Carbon Oxidation Globally
Článek Direct Monitoring of the Strand Passage Reaction of DNA Topoisomerase II Triggers Checkpoint Activation
Článek Multiple bHLH Proteins form Heterodimers to Mediate CRY2-Dependent Regulation of Flowering-Time in
Článek A Reversible Histone H3 Acetylation Cooperates with Mismatch Repair and Replicative Polymerases in Maintaining Genome Stability
Článek ALS-Associated Mutations Result in Compromised Alternative Splicing and Autoregulation
Článek Robust Demographic Inference from Genomic and SNP Data
Článek Preferential Binding to Elk-1 by SLE-Associated Risk Allele Upregulates Expression
Článek Rad52 Sumoylation Prevents the Toxicity of Unproductive Rad51 Filaments Independently of the Anti-Recombinase Srs2
Článek The Serum Resistome of a Globally Disseminated Multidrug Resistant Uropathogenic Clone
Článek Identification of 526 Conserved Metazoan Genetic Innovations Exposes a New Role for Cofactor E-like in Neuronal Microtubule Homeostasis
Článek SUMO Localizes to the Central Element of Synaptonemal Complex and Is Required for the Full Synapsis of Meiotic Chromosomes in Budding Yeast
Článek Integrated Enrichment Analysis of Variants and Pathways in Genome-Wide Association Studies Indicates Central Role for IL-2 Signaling Genes in Type 1 Diabetes, and Cytokine Signaling Genes in Crohn's Disease
Článek Genome-Wide High-Resolution Mapping of UV-Induced Mitotic Recombination Events in
Článek Genome-Wide Analysis of Cell Type-Specific Gene Transcription during Spore Formation in
Článek Playing the Field: Sox10 Recruits Different Partners to Drive Central and Peripheral Myelination
Článek Two Portable Recombination Enhancers Direct Donor Choice in Fission Yeast Heterochromatin
Článek Mining the Human Phenome Using Allelic Scores That Index Biological Intermediates
Článek A Minimal Nitrogen Fixation Gene Cluster from sp. WLY78 Enables Expression of Active Nitrogenase in
Článek A Review of Bacteria-Animal Lateral Gene Transfer May Inform Our Understanding of Diseases like Cancer
Článek High Throughput Sequencing Reveals Alterations in the Recombination Signatures with Diminishing Spo11 Activity
Článek Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
Článek Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer
Článek A GDF5 Point Mutation Strikes Twice - Causing BDA1 and SYNS2
Článek Systematic Unraveling of the Unsolved Pathway of Nicotine Degradation in
Článek Natural Genetic Variation of Integrin Alpha L () Modulates Ischemic Brain Injury in Stroke
Článek Evolutionary Tuning of Protein Expression Levels of a Positively Autoregulated Two-Component System
Článek Evolutionary Change within a Bipotential Switch Shaped the Sperm/Oocyte Decision in Hermaphroditic Nematodes
Článek Limiting of the Innate Immune Response by SF3A-Dependent Control of MyD88 Alternative mRNA Splicing
Článek Multiple Signaling Pathways Coordinate to Induce a Threshold Response in a Chordate Embryo
Článek Distinct Regulatory Mechanisms Act to Establish and Maintain Pax3 Expression in the Developing Neural Tube
Článek Genome Wide Analysis of Narcolepsy in China Implicates Novel Immune Loci and Reveals Changes in Association Prior to Versus After the 2009 H1N1 Influenza Pandemic
Článek Mismatch Repair Genes and Modify CAG Instability in Huntington's Disease Mice: Genome-Wide and Candidate Approaches
Článek The Histone H3 K27 Methyltransferase KMT6 Regulates Development and Expression of Secondary Metabolite Gene Clusters
Článek Hsp70-Hsp40 Chaperone Complex Functions in Controlling Polarized Growth by Repressing Hsf1-Driven Heat Stress-Associated Transcription
Článek Function and Evolution of DNA Methylation in
Článek Stimulation of mTORC1 with L-leucine Rescues Defects Associated with Roberts Syndrome
Článek Transcription Termination and Chimeric RNA Formation Controlled by FPA
Článok vyšiel v časopise

PLOS Genetics

2013 Číslo 10
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

nový kurz
Autori: doc. MUDr. David Zemánek, Ph.D., MUDr. Anna Chaloupka, Ph.D.
Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#