#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
preLekára.sk / Odborné časopisy / PLOS Genetics / 2014 - 5

dGTP Starvation in Provides New Insights into the Thymineless-Death Phenomenon

English version České info

Starvation of cells for DNA precursor dTTP is strikingly lethal in many organisms, like bacteria, yeast, and human cells. This type of death is unusual in that starvation for other nutritional requirements generally results in growth arrest, but not in death. The phenomenon is called thymineless death (TLD), because it was first observed some 60 years ago when a thymine-requiring (thyA) E. coli strain was exposed to growth medium lacking thymine. The TLD phenomenon is of significant interest as it is the basis for several chemotherapeutic (anticancer) treatments in which rapidly growing cells are selectively killed by depletion of the cellular dTTP pool. The precise mechanisms by which cells succumb to dTTP depletion are of significant interest, but have remained elusive for a long time. In the present work, we demonstrate for the first time that the effect is not specific for dTTP starvation. We show that an E. coli strain starved for the DNA precursor dGTP dies in a manner similar to dTTP-starved cells. The effect, which we have termed dGTP starvation, might be exploited -⁠ like TLD -⁠ therapeutically.

Vyšlo v časopise: dGTP Starvation in Provides New Insights into the Thymineless-Death Phenomenon. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004310
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004310

Souhrn

Starvation of cells for DNA precursor dTTP is strikingly lethal in many organisms, like bacteria, yeast, and human cells. This type of death is unusual in that starvation for other nutritional requirements generally results in growth arrest, but not in death. The phenomenon is called thymineless death (TLD), because it was first observed some 60 years ago when a thymine-requiring (thyA) E. coli strain was exposed to growth medium lacking thymine. The TLD phenomenon is of significant interest as it is the basis for several chemotherapeutic (anticancer) treatments in which rapidly growing cells are selectively killed by depletion of the cellular dTTP pool. The precise mechanisms by which cells succumb to dTTP depletion are of significant interest, but have remained elusive for a long time. In the present work, we demonstrate for the first time that the effect is not specific for dTTP starvation. We show that an E. coli strain starved for the DNA precursor dGTP dies in a manner similar to dTTP-starved cells. The effect, which we have termed dGTP starvation, might be exploited -⁠ like TLD -⁠ therapeutically.

Zdroje

1. AhmadSI, KirkSH, EisenstarkA (1998) Thymine metabolism and thymineless death in prokaryotes and eukaryotes. Annu Rev Microbiol 52 : 591–625.

2. CohenSS, BarnerHD (1954) Studies on unbalanced growth in Escherichia coli. Proc Natl Acad Sci USA 40 : 885–893.

3. McGuireJJ (2003) Anticancer antifolates: current status and future directions. Curr Pharm Des 9 : 2593–2613.

4. LongleyDB, HarkinDP, JohnstonPG (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3 : 330–338.

5. FonvilleNC, BatesD, HastingsPJ, HanawaltPC, RosenbergSM (2010) Role of RecA and the SOS response in thymineless death in Escherichia coli. PLoS Genet 6(3): e1000865.

6. SangurdekarDP, et al. (2010) Thymineless death is associated with loss of essential genetic information from the replication origin. Mol Microbiol 75 : 1455–1467.

7. MartinCM, GuzmanEC (2011) DNA replication initiation as a key element in thymineless death. DNA Repair 10 : 94–101.

8. KuongKJ, KuzminovA (2010) Stalled replication fork repair and misrepair during thymineless death in Escherichia coli. Genes Cells 15 : 619–634.

9. KuongKJ, KuzminovA (2012) Disintegration of nascent replication bubbles during thymine starvation triggers RecA -⁠ and RecBCD-dependent replication origin destruction. J Biol Chem 287 : 23958–23970.

10. PritchardRH, LarkKG (1964) Induction of replication by thymine starvation at the chromosome origin in Escherichia coli. J Mol Biol 9 : 288–307.

11. Eriksson S, Sjöberg BM (1989) Ribonucleotide Reductase. In Allosteric Enzymes Hervé G ed (CRC press Inc), pp 189–215.

12. Neuhard J, Kelln RA (1996) Biosynthesis and conversion of pyrimidines. In Escherichia coli and Salmonella: cellular and molecular biology. Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE, editors. Washington, D.C: American Society for Microbiology. pp 580–599.

13. KornbergSR, LehmanIR, BessmanMJ, SimmsES, KornbergA (1958) Enzymatic cleavage of deoxyguanosine triphosphate to deoxyguanosine and tripolyphosphate. J Biol Chem 233 : 159–162.

14. QuirkS, BhatnagarSK, BessmanMJ (1990) Primary structure of the deoxyguanosine triphosphate triphosphohydrolase-encoding gene (dgt) of Escherichia coli. Gene 89 : 13–18.

15. GawelD, HamiltonMD, SchaaperRM (2008) A novel mutator of Escherichia coli carrying a defect in the dgt gene, encoding a dGTP triphosphohydrolase. J Bacteriol 190 : 6931–6939.

16. BeauchampBB, RichardsonCC (1988) A unique deoxyguanosine triphosphatase is responsible for the optA1 phenotype of Escherichia coli. Proc Natl Acad Sci USA 85 : 2563–2567.

17. MeyersJA, BeauchampBB, RichardsonCC (1987) Gene 1.2 protein of bacteriophage T7. Effect on deoxyribonucleotide pools. J Biol Chem 262 : 5288–5292.

18. Miller JA (1992) Short Course in Bacterial Genetics (Cold Spring Harbor Laboratory, NY).

19. DeoSS, TsengWC, SainiR, ColesRS, AthwalRS (1985) Purification and characterization of Escherichia coli xanthine-guanine phosphoribosyltransferase produced by plasmid pSV2gpt. Biochim Biophys Acta 8 : 233–239.

20. MengLM, NygaardP (1990) Identification of hypoxanthine and guanine as the co-repressors for the purine regulon genes of Escherichia coli. Mol Microbiol 4 : 2187–2192.

21. ChoBK, et al. (2011) The PurR regulon in Escherichia coli K-12 MG1655. Nucleic Acids Res 39 : 6456–6464.

22. BremerH, ChurchwardG (1977) An examination of the Cooper-Helmstetter theory of DNA replication in bacteria and its underlying assumptions. J Theor Biol 69 : 645–654.

23. SkarstadK, BoyeE, SteenHB (1986) Timing of initiation of chromosome replication in individual Escherichia coli cells. EMBO J 5 : 1711–1717.

24. ShinagawaH, KatoT, IseT, MakinoK, NakataA (1983) Cloning and characterization of the umu operon responsible for inducible mutagenesis in Escherichia coli. Gene 23 : 167–174.

25. BotelloE, Jiménez-SánchezA (1997) A temperature upshift induces initiation of replication at oriC on the Escherichia coli chromosome. Mol Microbiol 26 : 133–144.

26. OhkawaT (1975) Studies of intracellular thymidine nucleotides. Thymineless death and the recovery after re-addition of thymine in Escherichia coli K 12. Eur J Biochem 60 : 57–66.

27. MichelB, BoubakriH, BaharogluZ, LeMassonM, LestiniR (2007) Recombination proteins and rescue of arrested replication forks. DNA Repair (Amst) 6 : 967–80.

28. NeuhardJ, ThomassenE (1971) Turnover of the deoxyribonucleoside triphosphates in Escherichia coli 15 T during thymine starvation. Eur J Biochem 20 : 36–43.

29. ZaritskyA, WoldringhCL, EinavM, AlexeevaS (2006) Use of thymine limitation and thymine starvation to study bacterial physiology and cytology. J Bacteriol 188 : 1667–1679.

30. FishovI, ZaritskyA, GroverNB (1995) On microbial states of growth. Mol Microbiol 15 : 789–794.

31. HelmstetterCE, CooperS, PierucciO, RevelasE (1968) On the bacterial life sequences. Cold Spring Harbor Symp Quant Biol 33 : 809–822.

32. SueokaN, YoshikawaH (1965) The chromosome of Bacillus subtilis. I. The theory of marker frequency analysis. Genetics 52 : 747–757.

33. BirdRE, LouarnJ, MartuscelliJ, CaroL (1972) Origin and sequence of chromosome replication in Escherichia coli. J Mol Biol 70 : 549–566.

34. ZaritskyA, WoldringhCL (1978) Chromosome replication rate and cell shape in Escherichia coli: lack of coupling. J Bacteriol 135 : 581–587.

35. SimmonsLA, BreierAM, CozzarelliNR, KaguniJM (2004) Hyperinitiation of DNA replication in Escherichia coli leads to replication fork collapse and inviability. Mol Microbiol 51 : 349–358.

36. ZaritskyA, VischerN, RabinovitchA (2007) Changes of initiation mass and cell dimensions by the ‘eclipse’. Mol Microbiol 63 : 15–21.

37. NordströmK (1983) Replication of plasmid R1: Meselson-Stahl density shift experiments revisited. Plasmid 9 : 218–221.

38. AhluwaliaD, BienstockRJ, SchaaperRM (2012) Novel mutator mutants of E. coli nrdAB ribonucleotide reductase: insight into allosteric regulation and control of mutation rates. DNA Repair 5 : 480–487.

39. SchaaperRM, MathewsCK (2013) Mutational consequences of dNTP pool imbalances in E. coli. DNA Repair (Amst) 12 : 73–79.

40. MaaloeO, HanawaltPC (1961) Thymine deficiency and the normal DNA replication cycle. I. J Mol Biol 3 : 144–155.

41. HanawaltPC (1963) Involvement of synthesis of RNA in thymineless death. Nature 198 : 286.

42. BouvierF, SicardN (1975) Interference of dna ts mutations of Escherichia coli with thymineless death. J Bacteriol 124 : 1198–1204.

43. ItskoM, SchaaperRM (2011) The dgt gene of Escherichia coli facilitates thymine utilization in thymine-requiring strains. Mol Microbiol 81 : 1221–1232.

44. WheelerLJ, RajagopalI, MathewsCK (2005) Stimulation of mutagenesis by proportional deoxyribonucleoside triphosphate accumulation in Escherichia coli. DNA Repair 4 : 1450–1456.

45. GoldstoneDC, et al. (2011) HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. Nature 480 : 379–382.

46. PowellRD, HollandPJ, HollisT, PerrinoFW (2011) Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP-regulated deoxynucleotide triphosphohydrolase. J Biol Chem 286 : 43596–43600.

47. DatsenkoKA, WannerBL (2000) One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci USA 97 : 6640–6645.

48. VogelHJ, BonnerDM (1956) Acetylornithinase of Escherichia coli: partial purification and some properties. J Biol Chem 218 : 97–106.

49. StokkeC, FlåttenI, SkarstadK (2012) An easy-to-use simulation program demonstrates variations in bacterial cell cycle parameters depending on medium and temperature. PLoS One 7(2): e30981 doi:10.1371/journal.pone.0030981

50. MuzyczkaN, PolandRL, BessmanMJ (1972) Studies on the biochemical basis of spontaneous mutation. I. A comparison of the deoxyribonucleic acid polymerases of mutator, antimutator, and wild type strains of bacteriophage T4. J Biol Chem 247 : 7116–7122.

51. GaussP, DohertyDH, GoldL (1983) Bacterial and phage mutations that reveal helix-unwinding activities required for bacteriophage T4 DNA replication. Proc Natl Acad Sci USA 80 : 1669–1673.

52. Hove-JensenB, NygaardP (1989) Role of guanosine kinase in the utilization of guanosine for nucleotide synthesis in Escherichia coli. J Gen Microbiol 13 : 1263–1273.

Štítky
Genetika Reprodukčná medicína
Článek Genetic Interactions Involving Five or More Genes Contribute to a Complex Trait in Yeast
Článek A Mutation in the Gene in Dogs with Hereditary Footpad Hyperkeratosis (HFH)
Článek Loss of Function Mutation in the Palmitoyl-Transferase HHAT Leads to Syndromic 46,XY Disorder of Sex Development by Impeding Hedgehog Protein Palmitoylation and Signaling
Článek Heterogeneity in the Frequency and Characteristics of Homologous Recombination in Pneumococcal Evolution
Článek Genome-Wide Nucleosome Positioning Is Orchestrated by Genomic Regions Associated with DNase I Hypersensitivity in Rice
Článek Null Mutation in PGAP1 Impairing Gpi-Anchor Maturation in Patients with Intellectual Disability and Encephalopathy
Článek Single Nucleotide Variants in Transcription Factors Associate More Tightly with Phenotype than with Gene Expression
Článek Ribosomal Protein Mutations Induce Autophagy through S6 Kinase Inhibition of the Insulin Pathway
Článek Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human Diseases
Článek Epistatically Interacting Substitutions Are Enriched during Adaptive Protein Evolution
Článek Meiotic Drive Impacts Expression and Evolution of X-Linked Genes in Stalk-Eyed Flies
Článek G×G×E for Lifespan in : Mitochondrial, Nuclear, and Dietary Interactions that Modify Longevity
Článek Population Genomic Analysis of Ancient and Modern Genomes Yields New Insights into the Genetic Ancestry of the Tyrolean Iceman and the Genetic Structure of Europe
Článek p53 Requires the Stress Sensor USF1 to Direct Appropriate Cell Fate Decision
Článek Whole Exome Re-Sequencing Implicates and Cilia Structure and Function in Resistance to Smoking Related Airflow Obstruction
Článek Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues
Článek R-loops Associated with Triplet Repeat Expansions Promote Gene Silencing in Friedreich Ataxia and Fragile X Syndrome
Článek PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix
Článek The Impairment of MAGMAS Function in Human Is Responsible for a Severe Skeletal Dysplasia
Článek Octopamine Neuromodulation Regulates Gr32a-Linked Aggression and Courtship Pathways in Males
Článek Mlh2 Is an Accessory Factor for DNA Mismatch Repair in
Článek Activating Transcription Factor 6 Is Necessary and Sufficient for Alcoholic Fatty Liver Disease in Zebrafish
Článek The Spatiotemporal Program of DNA Replication Is Associated with Specific Combinations of Chromatin Marks in Human Cells
Článek Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts
Článek Genome-Wide Inference of Ancestral Recombination Graphs
Článek Mutations in Four Glycosyl Hydrolases Reveal a Highly Coordinated Pathway for Rhodopsin Biosynthesis and N-Glycan Trimming in
Článek SHP2 Regulates Chondrocyte Terminal Differentiation, Growth Plate Architecture and Skeletal Cell Fates
Článek The Impact of Population Demography and Selection on the Genetic Architecture of Complex Traits
Článek Retinoid-X-Receptors (α/β) in Melanocytes Modulate Innate Immune Responses and Differentially Regulate Cell Survival following UV Irradiation
Článek Genetic Dissection of the Female Head Transcriptome Reveals Widespread Allelic Heterogeneity
Článek Genome Sequencing and Comparative Genomics of the Broad Host-Range Pathogen AG8
Článek Copy Number Variation Is a Fundamental Aspect of the Placental Genome
Článek GOLPH3 Is Essential for Contractile Ring Formation and Rab11 Localization to the Cleavage Site during Cytokinesis in
Článek Hox Transcription Factors Access the RNA Polymerase II Machinery through Direct Homeodomain Binding to a Conserved Motif of Mediator Subunit Med19
Článek Drosha Promotes Splicing of a Pre-microRNA-like Alternative Exon
Článek Predicting the Minimal Translation Apparatus: Lessons from the Reductive Evolution of
Článek PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF
Článek Enhanced Interaction between Pseudokinase and Kinase Domains in Gcn2 stimulates eIF2α Phosphorylation in Starved Cells
Článek A HECT Ubiquitin-Protein Ligase as a Novel Candidate Gene for Altered Quinine and Quinidine Responses in
Článek Phosphorylation Modulates Clearance of Alpha-Synuclein Inclusions in a Yeast Model of Parkinson's Disease
Článek RPM-1 Uses Both Ubiquitin Ligase and Phosphatase-Based Mechanisms to Regulate DLK-1 during Neuronal Development
Článek More of a Good Thing or Less of a Bad Thing: Gene Copy Number Variation in Polyploid Cells of the Placenta
Článek More of a Good Thing or Less of a Bad Thing: Gene Copy Number Variation in Polyploid Cells of the Placenta
Článek Heritable Transmission of Stress Resistance by High Dietary Glucose in
Článek Revertant Mutation Releases Confined Lethal Mutation, Opening Pandora's Box: A Novel Genetic Pathogenesis
Článek Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification
Článek A Genome-Wide Assessment of the Role of Untagged Copy Number Variants in Type 1 Diabetes
Článek Selectivity in Genetic Association with Sub-classified Migraine in Women
Článek A Lack of Parasitic Reduction in the Obligate Parasitic Green Alga
Článek The Proper Splicing of RNAi Factors Is Critical for Pericentric Heterochromatin Assembly in Fission Yeast
Článek Discovery and Functional Annotation of SIX6 Variants in Primary Open-Angle Glaucoma
Článek Six Homeoproteins and a linc-RNA at the Fast MYH Locus Lock Fast Myofiber Terminal Phenotype
Článek EDR1 Physically Interacts with MKK4/MKK5 and Negatively Regulates a MAP Kinase Cascade to Modulate Plant Innate Immunity
Článek Genes That Bias Mendelian Segregation
Článek The Case for Junk DNA
Článek An In Vivo EGF Receptor Localization Screen in Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling
Článek Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder
Článek Hyperactivated Wnt Signaling Induces Synthetic Lethal Interaction with Rb Inactivation by Elevating TORC1 Activities
Článek Mutations in the Cholesterol Transporter Gene Are Associated with Excessive Hair Overgrowth
Článek Scribble Modulates the MAPK/Fra1 Pathway to Disrupt Luminal and Ductal Integrity and Suppress Tumour Formation in the Mammary Gland
Článek A Novel CH Transcription Factor that Regulates Expression Interdependently with GliZ in
Článek Phosphorylation of a WRKY Transcription Factor by MAPKs Is Required for Pollen Development and Function in
Článek Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics
Článek Spermatid Cyst Polarization in Depends upon and the CPEB Family Translational Regulator
Článek Insights into the Genetic Structure and Diversity of 38 South Asian Indians from Deep Whole-Genome Sequencing
Článek Intron Retention in the 5′UTR of the Novel ZIF2 Transporter Enhances Translation to Promote Zinc Tolerance in
Článek A Dominant-Negative Mutation of Mouse Causes Glaucoma and Is Semi-lethal via LBD1-Mediated Dimerisation
Článek Biased, Non-equivalent Gene-Proximal and -Distal Binding Motifs of Orphan Nuclear Receptor TR4 in Primary Human Erythroid Cells
Článek Ras-Mediated Deregulation of the Circadian Clock in Cancer
Článek Retinoic Acid-Related Orphan Receptor γ (RORγ): A Novel Participant in the Diurnal Regulation of Hepatic Gluconeogenesis and Insulin Sensitivity
Článek Extensive Diversity of Prion Strains Is Defined by Differential Chaperone Interactions and Distinct Amyloidogenic Regions
Článek Fine Tuning of the UPR by the Ubiquitin Ligases Siah1/2
Článek Paternal Poly (ADP-ribose) Metabolism Modulates Retention of Inheritable Sperm Histones and Early Embryonic Gene Expression
Článek Allele-Specific Genome-wide Profiling in Human Primary Erythroblasts Reveal Replication Program Organization
Článok vyšiel v časopise

PLOS Genetics

2014 Číslo 5
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#