1887

Abstract

Mycobacteria are an important group of human pathogens. Although the DNA repair mechanisms in mycobacteria are not well understood, these are vital for the pathogen's persistence in the host macrophages. In this study, we generated a null mutation in the gene of to allow us to compare the significance of the nucleotide excision repair (NER) pathway with two important base excision repair pathways, initiated by uracil DNA glycosylase (Ung) and formamidopyrimidine DNA glycosylase (Fpg or MutM), in an isogenic strain background. The strain deficient in NER was the most sensitive to commonly encountered DNA-damaging agents such as UV, low pH, reactive oxygen species, hypoxia, and was also sensitive to acidified nitrite. Taken together with previous observations on NER-deficient , these results suggest that NER is an important DNA repair pathway in mycobacteria.

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2008-09-01
2019-12-15
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References

  1. Asad, L. M. B. O., Medeiros, D. C., Felzenszwalb, I., Leitão, A. C. & Asad, N. R. ( 2000; ). Participation of stress-inducible systems and enzymes involved in BER and NER in the protection of Escherichia coli against cumene hydroperoxide. Mutat Res 461, 31–40.[CrossRef]
    [Google Scholar]
  2. Bailly, V., Verly, W. G., O'Connor, T. & Laval, J. ( 1989; ). Mechanisms of DNA strand nicking at apurinic/apyrimidinic sites by Escherichia coli [formamidopyrimidine]DNA glycosylase. Biochem J 262, 581–589.
    [Google Scholar]
  3. Boshoff, H. I., Reed, M. B., Barry, C. E., III & Mizrahi, V. ( 2003; ). DnaE2 polymerase contributes to in vivo survival and the emergence of drug resistance in Mycobacterium tuberculosis. Cell 113, 183–193.[CrossRef]
    [Google Scholar]
  4. Cole, S. T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., Gordon, S. V., Eiglmeier, K., Gas, S. & other authors ( 1998; ). Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544.[CrossRef]
    [Google Scholar]
  5. Cole, S. T., Eiglmeier, K., Parkhill, J., James, K. D., Thomson, N. R., Wheeler, P. R., Honoré, N., Garnier, T., Churcher, C. & other authors ( 2001; ). Massive gene decay in the leprosy bacillus. Nature 409, 1007–1011.[CrossRef]
    [Google Scholar]
  6. Cooke, M. S., Evans, M. D., Dizdaroglu, M. & Lunec, J. ( 2003; ). Oxidative DNA damage: mechanisms, mutations and disease. FASEB J 17, 1195–1214.[CrossRef]
    [Google Scholar]
  7. Czeczot, H., Tudek, B., Lambert, B., Laval, J. & Boiteux, S. ( 1991; ). Escherichia coli Fpg protein and UvrABC endonuclease repair DNA damage induced by methylene blue plus visible light in vivo and in vitro. J Bacteriol 173, 3419–3424.
    [Google Scholar]
  8. Darwin, K. H. & Nathan, C. F. ( 2005; ). Role of nucleotide excision repair in virulence of Mycobacterium tuberculosis. Infect Immun 73, 4581–4587.[CrossRef]
    [Google Scholar]
  9. Darwin, K. H., Ehrt, S., Gutierrez-Ramos, J. C., Weich, N. & Nathan, C. F. ( 2003; ). The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 302, 1963–1966.[CrossRef]
    [Google Scholar]
  10. David, H. L. ( 1970; ). Probability distribution of drug-resistant mutants in unselected populations of Mycobacterium tuberculosis. Appl Microbiol 20, 810–814.
    [Google Scholar]
  11. Dick, T., Lee, B. H. & Oei, B. M. ( 1998; ). Oxygen depletion induced dormancy in Mycobacterium smegmatis. FEMS Microbiol Lett 163, 159–164.[CrossRef]
    [Google Scholar]
  12. Duncan, B. K. ( 1981; ). DNA glycosylases. In The Enzymes, pp. 565–586. Edited by P. Boyer. Orlando: Academic Press.
  13. Graham, J. E. & Clark-Curtiss, J. E. ( 1999; ). Identification of Mycobacterium tuberculosis RNAs synthesized in response to phagocytosis by human macrophages by selective capture of transcribed sequences (SCOTS). Proc Natl Acad Sci U S A 96, 11554–11559.[CrossRef]
    [Google Scholar]
  14. Graves, R. J., Felzenszwalb, I., Laval, J. & O'Connor, T. R. ( 1992; ). Excision of 5′-terminal deoxyribose phosphate from damaged DNA is catalyzed by the Fpg protein of Escherichia coli. J Biol Chem 267, 14429–14435.
    [Google Scholar]
  15. Grishko, V., Solomon, M., Breit, J. F., Killilea, D. W., Ledoux, S. P., Wilson, G. L. & Gillespie, M. N. ( 2001; ). Hypoxia promotes oxidative base modifications in the pulmonary artery endothelial cell VEGF gene. FASEB J 15, 1267–1269.
    [Google Scholar]
  16. Hall, B. G. ( 1995; ). Genetics of selection induced mutations. I. uvrA, uvrB, uvrC, and uvrD are selection induced specific mutator loci. J Mol Evol 40, 86–93.[CrossRef]
    [Google Scholar]
  17. Hartman, P. E., Ames, B. N., Roth, J. R., Barnes, W. M. & Levin, D. E. ( 1986; ). Target sequences for mutagenesis in Salmonella histidine-requiring mutants. Environ Mutagen 8, 631–641.[CrossRef]
    [Google Scholar]
  18. Hatfull, G. F. & Jacobs, W. B. ( 2002; ). Molecular Genetics of Mycobacteria. Washington, DC: American Society for Microbiology.
  19. Huang, S., Kang, J. & Blaser, M. J. ( 2006; ). Antimutator role of the DNA glycosylase mutY gene in Helicobacter pylori. J Bacteriol 188, 6224–6234.[CrossRef]
    [Google Scholar]
  20. Jain, R., Kumar, P. & Varshney, U. ( 2007; ). A distinct role of formamidopyrimidine DNA glycosylase (MutM) in down-regulation of accumulation of G, C mutations and protection against oxidative stress in mycobacteria. DNA Repair (Amst) 6, 1774–1785.[CrossRef]
    [Google Scholar]
  21. Kenney, T. J. & Churchward, G. ( 1996; ). Genetic analysis of the Mycobacterium smegmatis rpsL promoter. J Bacteriol 178, 3564–3571.
    [Google Scholar]
  22. Kow, Y. W., Wallace, S. S. & Houten, B. V. ( 1990; ). UvrABC nuclease complex repairs thymine glycol, an oxidative DNA base damage. Mutat Res 235, 147–156.[CrossRef]
    [Google Scholar]
  23. Krokan, H. E., Standal, R. & Slupphaug, G. ( 1997; ). DNA glycosylases in the base excision repair of DNA. Biochem J 325, 1–16.
    [Google Scholar]
  24. Kuraoka, I., Bender, C., Romieu, A., Cadet, J., Wood, R. D. & Lindahl, T. ( 2000; ). Removal of oxygen free-radical-induced 5′,8-purine cyclodeoxynucleosides from DNA by the nucleotide excision-repair pathway in human cells. Proc Natl Acad Sci U S A 97, 3832–3837.[CrossRef]
    [Google Scholar]
  25. Lancaster, J. R., Jr ( 1997; ). A tutorial on the diffusibility and reactivity of free nitric oxide. Nitric Oxide 1, 18–30.[CrossRef]
    [Google Scholar]
  26. Lin, J. J. & Sancar, A. ( 1989; ). A new mechanism for repairing oxidative damage to DNA: (A)BC excinuclease removes AP sites and thymine glycols from DNA? Biochemistry 28, 7979–7984.[CrossRef]
    [Google Scholar]
  27. Lindahl, T. ( 1979; ). DNA glycosylases, endonucleases for apurinic/apyrimidinic sites, and base excision-repair. Prog Nucleic Acid Res Mol Biol 22, 135–192.
    [Google Scholar]
  28. Manganelli, R., Provvedi, R., Rodrigue, S., Beaucher, J., Gaudreau, L. & Smith, I. ( 2004; ). Sigma factors and global gene regulation in Mycobacterium tuberculosis. J Bacteriol 186, 895–902.[CrossRef]
    [Google Scholar]
  29. Mayuri, Bagchi, G, Das, T. K. & Tyagi, J. S. ( 2002; ). Molecular analysis of the dormancy response in Mycobacterium smegmatis: expression analysis of genes encoding the DevR-DevS two-component system, Rv3134c and chaperon α-crystallin homologues. FEMS Microbiol Lett 211, 231–237.
    [Google Scholar]
  30. Mizrahi, V. & Andersen, S. J. ( 1998; ). DNA repair in Mycobacterium tuberculosis. What have we learnt from the genome sequence? Mol Microbiol 29, 1331–1339.[CrossRef]
    [Google Scholar]
  31. Moller, P., Loft, S., Lundby, C. & Olsen, N. V. ( 2001; ). Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA damage in humans. FASEB J 15, 1181–1186.[CrossRef]
    [Google Scholar]
  32. O'Brien, L., Carmichael, J., Lowrie, D. B. & Andrew, P. W. ( 1994; ). Strains of Mycobacterium tuberculosis differ in susceptibility to reactive nitrogen intermediates in vitro. Infect Immun 62, 5187–5190.
    [Google Scholar]
  33. Pelicic, V., Jackson, M., Reyrat, J. M., Jacobs, W. R., Jr, Gicquel, B. & Guilhot, C. ( 1997; ). Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 94, 10955–10960.[CrossRef]
    [Google Scholar]
  34. Pienkowska, M., Glickman, B. W., Ferreira, A., Anderson, M. & Zielenska, M. ( 1993; ). Large scale mutational analysis of EMS induced mutation in the lacI gene of Escherichia coli. Mutat Res 288, 123–131.[CrossRef]
    [Google Scholar]
  35. Rand, L., Hinds, J., Springer, B., Sander, P., Buxton, R. S. & Davis, E. O. ( 2003; ). The majority of inducible DNA repair genes in Mycobacterium tuberculosis are induced independently of RecA. Mol Microbiol 50, 1031–1042.[CrossRef]
    [Google Scholar]
  36. Reed, K. C. & Mann, D. A. ( 1985; ). Rapid transfer of DNA from agarose gels to nylon membranes. Nucleic Acids Res 13, 7207–7221.[CrossRef]
    [Google Scholar]
  37. Sambrook, J., Fritsch, E. F. & Maniatis, T. ( 1989; ). Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  38. Scott, A. D., Neishabury, M., Jones, D. H., Reed, S. H., Boiteux, S. & Waters, R. ( 1999; ). Spontaneous mutation, oxidative DNA damage, and the roles of base and nucleotide excision repair in the yeast Saccharomyces cerevisiae. Yeast 15, 205–218.[CrossRef]
    [Google Scholar]
  39. Shapiro, R., Dubelman, S., Feinberg, A. M., Crain, P. F. & McCloskey, J. A. ( 1977; ). Isolation and identification of cross-linked nucleosides from nitrous acid treated deoxyribonucleic acid. J Am Chem Soc 99, 302–303.[CrossRef]
    [Google Scholar]
  40. Skorvaga, M., Theis, K., Mandavilli, B. S., Kisker, C. & Van Houten, B. ( 2002; ). The beta-hairpin motif of UvrB is essential for DNA binding, damage processing, and UvrC-mediated incisions. J Biol Chem 277, 1553–1559.[CrossRef]
    [Google Scholar]
  41. Smith, D. R., Richterich, P., Rubenfield, M., Rice, P. W., Butler, C., Lee, H. M., Kirst, S., Gundersen, K., Abendschan, K. & other authors ( 1997; ). Multiplex sequencing of 1.5 Mb of the Mycobacterium leprae genome. Genome Res 7, 802–819.
    [Google Scholar]
  42. Snapper, S. B., Melton, R. E., Mustafa, S., Kieser, T. & Jacobs, W. R., Jr ( 1990; ). Isolation and characterization of efficient plasmid transformation mutants of Mycobacterium smegmatis. Mol Microbiol 4, 1911–1919.[CrossRef]
    [Google Scholar]
  43. Stover, C. K., de la Cruz, V. F., Fuerst, T. R., Burlein, J. E., Benson, L. A., Bennett, L. T., Bansal, G. P., Young, J. F., Lee, M. H. & other authors ( 1991; ). New use of BCG for recombinant vaccines. Nature 351, 456–460.[CrossRef]
    [Google Scholar]
  44. Stuehr, D. J., Gross, S. S., Sakuma, I., Levi, R. & Nathan, C. F. ( 1989; ). Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium-derived relaxing factor and the chemical reactivity of nitric oxide. J Exp Med 169, 1011–1020.[CrossRef]
    [Google Scholar]
  45. Tamir, S., Burney, S. & Tannenbaum, S. R. ( 1996; ). DNA damage by nitric oxide. Chem Res Toxicol 9, 821–827.[CrossRef]
    [Google Scholar]
  46. Tchou, J., Kasai, H., Shibutani, S., Chung, M. H., Laval, J., Grollman, A. P. & Nishimura, S. ( 1991; ). 8-Oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity. Proc Natl Acad Sci U S A 88, 4690–4694.[CrossRef]
    [Google Scholar]
  47. Vasanthakrishna, M., Kumar, N. V. & Varshney, U. ( 1997; ). Characterization of the initiator tRNA gene locus and identification of a strong promoter from Mycobacterium tuberculosis. Microbiology 143, 3591–3598.[CrossRef]
    [Google Scholar]
  48. Venkatesh, J., Kumar, P., Krishna, P. S., Manjunath, R. & Varshney, U. ( 2003; ). Importance of uracil DNA glycosylase in Pseudomonas aeruginosa and Mycobacterium smegmatis, G+C-rich bacteria, in mutation prevention, tolerance to acidified nitrite, and endurance in mouse macrophages. J Biol Chem 278, 24350–24358.[CrossRef]
    [Google Scholar]
  49. Vieira, J. & Messing, J. ( 1982; ). The pUC plasmids, an M13 mp-7 derived system for insertion mutagenesis and sequencing with universal primers. Gene 19, 259–268.[CrossRef]
    [Google Scholar]
  50. Wayne, L. G. & Hayes, L. G. ( 1996; ). An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicative persistence. Infect Immun 64, 2062–2069.
    [Google Scholar]
  51. Wayne, L. G. & Lin, K.-Y. ( 1982; ). Glyoxylate metabolism and adaptation of Mycobacterium tuberculosis to survival under anaerobic conditions. Infect Immun 37, 1042–1049.
    [Google Scholar]
  52. Wink, D. A., Kasprzak, K. S., Maragos, C. M., Elespuru, R. K., Misra, M., Dunams, T. M., Cebula, T. A., Koch, W. H., Andrews, A. W. & other authors ( 1991; ). DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 254, 1001–1003.[CrossRef]
    [Google Scholar]
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