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


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.

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