Chapter 23 : Nucleic Acid Metabolism

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Nucleic Acid Metabolism, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817657/9781555812959_Chap23-1.gif /docserver/preview/fulltext/10.1128/9781555817657/9781555812959_Chap23-2.gif


The first part of this chapter reviews the biosynthesis, salvage, and interconversion of purine and pyrimidine ribonucleotides; the biosynthesis of deoxyribonucleotides; and the biosynthesis and function of (p)ppGpp in . The second part reviews the processes of DNA replication, repair, and mutagenesis in the context of the mechanisms of genome evolution, pathogenesis, and the development of drug resistance in . The genome sequence of confirmed that the de novo synthesis of purines is mediated by the same highly conserved pathways seen in other bacteria. Purine nucleotide phosphorylase catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. Ribonucleotide reductase (RNR), the two-subunit enzyme that catalyzes the reduction of nucleoside diphosphates to deoxynucleoside diphosphates, is responsible for the first committed step in DNA synthesis. This step is the rate-limiting step for replicating the genome and thus is an ideal candidate for drug targeting. All drug resistance in is mediated by the introduction of mutations in chromosomal genes, a significant proportion of which correspond to base substitution and frameshift mutations. Whole-genome expression profiling has provided exciting insights into the global response of to DNA damage. The development of increasingly powerful technologies for exploring protein function, structure, and expression in has led to a quantum leap in understanding nucleic acid metabolism in this organism.

Citation: Mizrahi V, Buckstein M, Rubin H. 2005. Nucleic Acid Metabolism, p 369-378. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch23
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Acharya, N.,, and U. Varshney. 2002. Biochemical properties of single-stranded DNA-binding protein from Mycobacterium smegmatis, a fast-growing mycobacterium and its physical interaction with uracil DNA glycosylases . J. Mol. Biol. 318: 1251 1264.
2. Arrigo, C. J.,, K. Singh,, and M. J. Modak. 2002. DNA polymerase I of Mycobacterium tuberculosis: functional role of a conserved aspartate in the hinge joining the M and N helices. J. Biol. Chem. 277: 1653 1661.
3. Avarbock, D.,, J. Salem,, L. S. Li,, Z. M. Wang,, and H. Rubin. 1999. Cloning and characterization of a bifunctional relA/ spot homologue from Mycobacterium tuberculosis. Gene 233: 261 269.
4. Avarbock, A.,, D. Avarbock,, and H. Rubin. 2000. Differential regulation of opposing Rel Mtb activities by the aminoacylation state of a tRNA ribosome mRNA Rel Mtb complex. Biochemistry 39: 11640 11648.
5. Banu, S.,, N. Honore,, B. Saint-Joanis,, D. Philpott,, M. C. Prevost,, and S. T. Cole. 2002. Are the PE-PGRS proteins of Mycobacterium tuberculosis variable surface antigens? Mol. Microbiol. 44: 9 19.
6. Boshoff, H. I. M.,, M. B. Reed,, C. E. Barry III,, and V. Mizrahi. 2003. dnaE2 contributes to in vivo survival and the emergence of drug resistance in Mycobacterium tuberculosis. Cell 113: 183 193.
7. Brooks, P. C.,, F. Movahedzadeh,, and E. O. Davis. 2001. Identification of some DNA damage-inducible genes of Mycobacterium tuberculosis: apparent lack of correlation with LexA binding. J. Bacteriol. 183: 4459 4467.
8. Brosch, R.,, A. S. Pym,, S. V. Gordon,, and S. T. Cole. 2001. The evolution of mycobacterial pathogenicity: clues from comparative genomics. Trends Microbiol. 9: 452 458.
9. Brosch, R.,, S. V. Gordon,, M. Marmiesse,, P. Brodin,, C. Buchrieser,, K. Eiglmeier,, T. Garnier,, C. Gutierrez,, G. Hewinson,, K. Kremer,, L. M. Parsons,, A. S. Pym,, S. Samper,, D. van Soolingen,, and S. T. Cole. 2002. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc. Natl. Acad. Sci. USA 99: 3684 3689.
10. Buchmeier, N. A.,, C. J. Lipps,, M. Y. So,, and F. Heffron. 1993. Recombination-deficient mutants of Salmonella typhimurium are avirulent and sensitive to the oxidative burst of macrophages. Mol. Microbiol. 7: 933 936.
11. Burns, B. P, S. L. Hazell, G. L. Mendz, T. Kolesnikow, D. Tillet, and B. A. Neilan. 2000. The Heliobacter pylori pyrB gene encoding aspartate carbamoyltransferase is essential for bacterial survival. Arch. Biochem. Biophys. 380: 78 84.
12. Chen, Y.,, S. Morera,, J. Mocan,, I. Lascu,, and J. Janin. 2002. X-ray structure of Mycobacterium tuberculosis nucleoside disphosphate kinase. Proteins 47: 556 557.
13. Chopra, P.,, A. Singh,, A. Koul,, S. Ramachandran,, K. Drlica,, A.K. Tyagi,, and Y. Singh. 2003. Cytotoxic activity of nucleoside diphosphate kinase secreted from Mycobacterium tuberculosis. Eur. J. Biochem. 270: 625 634.
14. Cole, S. T.,, R. Brosch,, J. Parkhill,, T. Garnier,, C. Churcher,, D. Harris,, S. V. Gordon,, K. Eiglmeier,, S. Gas,, C. E. Barry III,, F. Tekaia,, K. Badcock,, D. Basham,, D. Brown,, T. Chillingworth,, R. Connor,, R. Davies,, K. Devlin,, T. Feltwell,, S. Gentles,, N. Hamlin,, S. Holroyd,, T. Hornsby,, K. Jagels,, A. Krogh,, J. McLean,, S. Moule,, L. Murphy,, K. Oliver,, J. Osborne,, M. A. Quail,, M.-A. Rajandream,, J. Rogers,, S. Rutter,, K. Seeger,, J. Skelton,, R. Squares,, S. Squares,, J.E. Sulston,, K. Taylor,, S. Whitehead,, and B.G. Barrell. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393: 537 544.
15. Courcelle, J.,, A. Khodursky,, B. Peter,, P. O. Brown,, and P. C. Hanawalt. 2001. Comparative gene expression profiles following UV exposure in wild-type and SOS-deficient Escherichia coli. Genetics 158: 41 64.
16. Dahl, J. L.,, C. N. Kraus,, H. I. Boshoff,, B. Doan,, K. Foley,, D. Avarbock,, G. Kaplan,, V. Mizrahi,, H. Rubin,, and C. E. Barry III. 2003. The role of RelMTb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Proc. Natl. Acad. Sci. USA 100: 10026 10031.
17. Darwin, K. H.,, S. Ehrt,, J. C. Gutierrez-Ramos,, N. Weich,, and C. F. Nathan. 2003. The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 302: 1963 1966.
18. Datta, S.,, M. M. Prabu,, M. B. Vaze,, N. Ganesh,, N. R. Chandra,, K. Muniyappa,, and M. Vijayan. 2000. Crystal structures of Mycobacterium tuberculosis RecA and its complex with ADP-AIF4: implications for decreased ATPase activity and molecular aggregation. Nucleic Acids Res. 28: 4964 4973.
19. David, H. L. 1970. Probability distribution of drug-resistant mutants in unselected populations of Mycobacterium tuberculosis. Appl. Microbiol. 20: 810 814.
20. Davis, E. O.,, E. M. Dullaghan,, and L. Rand. 2002. Definition of the mycobacterial SOS box and use to identify LexA-regulated genes in Mycobacterium tuberculosis. J. Bacteriol. 184: 3287 3295.
21. Davis, E. O.,, B. Springer,, K. K. Gopaul,, K. G. Papavinasasundaram,, P. Sander,, and E. C. Böttger. 2002. DNA damage induction of recA in Mycobacterium tuberculosis independently of LexA. Mol. Microbiol. 46: 791 800.
22. Dawes, S. S.,, D. F. Warner,, L. Tsenova,, J. Timm,, J. D. Mc- Kinney,, G. Kaplan,, H. Rubin,, and V. Mizrahi. 2003. Ribonucleotide reduction in Mycobacterium tuberculosis: function and expression of genes encoding class Ib and class II ribonucleotide reductases . Infect. Immun. 71: 6124 6131.
23. Durbach, S. I.,, B. Springer,, E. E. Machowski,, R. J. North,, K. G. Papavinasasundaram,, M. J. Colston,, E. C. Böttger,, and V. Mizrahi. 2003. DNA alkylation damage as a sensor of nitrosative stress in Mycobacterium tuberculosis. Infect. Immun. 71: 997 1000.
24. Elleingand, E.,, C. Gerez,, S. Un,, M. Knupling,, G. Lu,, J. Salem,, H. Rubin,, S. Sauge-Merle,, J. P. Laulhere,, and M. Fontecave. 1998. Reactivity studies of the tyrosyl radical in ribonucleotide reductase from Mycobacterium tuberculosis and Arabidopsis thaliana—comparison with Escherichia coli and mouse. Eur. J. Biochem. 258: 485 490.
25. Espinal, M. A.,, S. J. Kim,, P. G. Suarez,, K. M. Kam,, A. G. Khomenko,, G. B. Migliori,, J. Baez,, A. Kochi,, C. Dye,, and M. C. Raviglione. 2000. Standard short-course chemotherapy for drug-resistant tuberculosis: treatment outcomes in 6 countries. JAMA 283: 2537 2545.
26. Fang, Z.,, C. Doig,, D. T. Kenna,, N. Smittipat,, P. Palittapongarnpim,, B. Watt,, and K. J. Forbes. 1999. IS6110-mediated deletions of wild-type chromosomes of Mycobacterium tuberculosis. J. Bacteriol. 181: 1014 1020.
27. Fleischmann, R. D.,, D. Alland,, J. A. Eisen,, L. Carpenter,, O. White,, J. Peterson,, R. DeBoy,, R. Dodson,, M. Gwinn,, D. Haft,, E. Hickey,, J. F. Kolonay,, W. C. Nelson,, L. A. Umayam,, M. Ermolaeva,, S. L. Salzberg,, A. Delcher,, T. Utterback,, J. Weidman,, H. Khouri,, J. Gill,, A. Mikula,, W. Bishai,, W. R. Jacobs, Jr.,, J. C. Venter,, and C. M. Fraser. 2002. Wholegenome comparison of Mycobacterium tuberculosis clinical and laboratory strains. J. Bacteriol. 184: 5479 5490.
28. Gentry, D. R.,, V. J. Hernandez,, L. H. Nguyen,, D. B. Jensen,, and M. Cashel. 1993. Synthesis of the stationary-phase sigma factor sigma s is positively regulated by ppGpp. J. Bacteriol. 175: 7982 7989.
29. Goodman, M. F. 2002. Error-prone repair DNA polymerases in prokaryotes and eukaryotes. Annu. Rev. Biochem. 71: 17 50.
30. Gordon, S. V.,, B. Heym,, J. Parkhill,, B. Barrell,, and S. Cole. 1999. New insertion sequences and a novel repeated sequence in the genome of Mycobacterium tuberculosis H37Rv. Microbiology 145: 881 892.
31. Guhan, N.,, and K. Muniyappa. 2002. The RecA intein of Mycobacterium tuberculosis promotes cleavage of ectopic DNA sites. Implications for the dispersal of inteins in natural populations. J. Biol. Chem. 277: 40352 40361.
32. Guhan, N.,, and K. Muniyappa. 2002. Mycobacterium tuberculosis RecA intein possesses a novel ATP-dependent site-specific double-stranded DNA endonuclease activity. J. Biol. Chem. 277: 16257 16264.
33. Haouz, A.,, V. Vanheusden,, H. Munier-Lehmann,, M. Froeyen,, P. Herdewijn,, S. Van Calenbergh,, and M. Delarue. 2003. Enzymatic and structural analysis of inhibitors designed against M. tuberculosis thymidylate kinase. New insights into the phosphoryl transfer mechanism. J. Biol. Chem. 278: 4963 4971.
34. Hinds, J.,, E. Mahenthiralingam,, K. E. Kempsell,, K. Duncan,, R. W. Stokes,, T. Parish,, and N. G. Stoker. 1999. Enhanced gene replacement in mycobacteria. Microbiology 145: 519 527.
35. Ho, T. B.,, B. D. Robertson,, G. M. Taylor,, R. J. Shaw,, and D. B. Young. 2000. Comparison of Mycobacterium tuberculosis genomes reveals frequent deletions in a 20 kb variable region in clinical isolates. Yeast 17: 272 282.
36. Hu, Y. M.,, P. D. Butcher,, K. Sole,, D. A. Mitchison,, and A. R. Coates. 1998. Protein synthesis is shutdown in dormant Mycobacterium tuberculosis and is reversed by oxygen or heat shock. FEMS Microbiol. Lett. 158: 139 145.
37. Hughes, A. L.,, R. Friedman,, and M. Murray. 2002. Genomewide pattern of synonymous nucleotide substitution in two complete genomes of Mycobacterium tuberculosis. Emerg. Infect. Dis. 8: 1342 1346.
38. Kato-Maeda, M.,, J. T. Rhee,, T. R. Gingeras,, H. Salamon,, J. Drenkow,, N. Smittipat,, and P. M. Small. 2001. Comparing genomes within the species Mycobacterium tuberculosis. Genome Res. 11: 547 554.
39. Keer, J.,, M. J. Smeulders,, and H. D. Williams. 2001. A purF mutant of Mycobacterium smegmatis has impaired survival during oxygen-starved stationary phase. Microbiology 147: 473 481.
40. Khil, P. P.,, and R. D. Camerini-Otero. 2002. Over 1000 genes are involved in the DNA damage response of Escherichia coli. Mol. Microbiol. 44: 89 105.
41. LeClerc, J. E.,, B. Li,, W. L. Payne,, and T. A. Cebula. 1996. High mutation frequencies among Escherichia coli and Salmonella pathogens. Science 274: 1208 1211.
42. Li de la Sierra, I.,, H. Munier-Lehmann,, A. M. Gilles,, O. Barzu,, and M. Delarue. 2000. Crystallization and preliminary X-ray analysis of the thymidylate kinase from Mycobacterium tuberculosis. Acta Crystallogr. Ser. D. 56: 226 228.
43. Li de la Sierra, I.,, H. Munier-Lehmann,, A. M. Gilles,, O. Barzu,, and M. Delarue. 2001. X-ray structure of TMP kinase from Mycobacterium tuberculosis complexed with TMP at 1.95A resolution. J. Mol. Biol. 311: 87 100.
44. Liu, A.,, S. Potsch,, A. Davydov,, A. L. Barra,, H. Rubin,, and A. Graslund. 1998. The tyrosyl free radical of recombinant ribonucleotide reductase from Mycobacterium tuberculosis is located in a rigid hydrophobic pocket. Biochemistry 37: 16369 16477.
45. Makarova, K. S.,, L. Aravind,, N. V. Grishin,, I. B. Rogozin,, and E. V. Koonin. 2002. A DNA repair system specific for theromophilic Archaea and bacteria predicted by genomic context analysis. Nucleic Acids Res. 30: 482 496.
46. Martinez-Costa, O. H.,, M. A. Fernandez-Moreno,, and F. Malpartida. 1998. The relA/ spoT-homologous gene in Streptomyces coelicolor encodes both ribosome-dependent (p)ppGppsynthesizing and -degrading activities. J. Bacteriol. 180: 4123 4132.
47. McAdam, R. A.,, S. Quan,, and C. Guilhot,. 2000. Mycobacterial transposons and their applications, p. 69 84. In G. F. Hatfull, and W. R. Jacobs, Jr. (ed.), Molecular Genetics of Mycobacteria. ASM Press, Washington, D.C.
48. McAdam, R. A.,, S. Quan,, D. A. Smith,, S. Bardarov,, J. C. Betts,, F. C. Cook,, E. U. Hooker,, A. P. Lewis,, P. Woollard,, M. J. Everett,, P. T. Lukey,, G. J. Bancroft,, W. R. Jacobs, Jr.,, and K. Duncan. 2002. Characterization of a Mycobacterium tuberculosis H37Rv transposon library reveals insertions in 351 ORFs and mutants with altered virulence. Microbiology 148: 2975 2986.
49. Mechold, U.,, H. Murphy,, L. Brown,, and M. Cashel. 2002. Intramolecular regulation of the opposing (p)ppGpp catalytic activities of Rel(Seq), the Rel/Spo enzyme from Streptococcus equisimilis. J. Bacteriol. 184: 2878 2888.
50. Mechold, U.,, and H. Malke. 1997. Characterization of the stringent and relaxed responses of Streptococcus equisimilis. J. Bacteriol. 17: 2658 2667.
51. Merino, D.,, H. Reglier-Poupet,, P. Berche,, A. Charbit, and The European Listeria Genome Consortium. 2002. A hypermutator phenotype attenuates the virulence of Listeria monocytogenes in a mouse model. Mol. Microbiol. 44: 877 887.
52. Metzgar, D.,, and C. Wills. 2000. Evidence for the adaptive evolution of mutation rates. Cell 101: 581 584.
53. Mizrahi, V.,, and S. J. Andersen. 1998. DNA repair in Mycobacterium tuberculosis. What have we learnt from the genome sequence? Mol. Microbiol. 29: 1331 1339.
54. Mizrahi, V.,, S. S. Dawes,, and H. Rubin,. 2000. DNA replication, p. 159 172. In G. F. Hatfull, and W. R. Jacobs, Jr. (ed.), Molecular Genetics of Mycobacteria. ASM Press, Washington, D.C.
55. Mostowy, S.,, D. Cousins,, J. Brinkman,, A. Aranaz,, and M. A. Behr. 2002. Genomic deletions suggest a phyogeny for the Mycobacterium tuberculosis complex . J. Infect. Dis. 186: 74 80.
56. Munier-Lehmann, H.,, S. Burlacu-Miron,, C. T. Craescu,, H. H. Mantsch,, and C. P. Schultz. 1999. A new subfamily of short bacterial adenylate kinases with the Mycobacterium tuberculosis enzyme as a model: a predictive and experimental study. Proteins 36: 238 248.
57. Muniyappa, K.,, M. B. Vaze,, N. Ganesh,, M. S. Reddy,, N. Guhan,, and R. Venkatesh. 2000. Comparative genomics of Mycobacterium tuberculosis and Escherichia coli for recombination ( rec) genes. Microbiology 146: 2093 2095.
58. Myllykallio, H.,, G. Lipowski,, D. Leduc,, J. Filee,, P. Forterre,, and U. Liebl. 2002. An alternative flavin-dependent mechanism for thymidylate synthesis. Science 297: 105 107.
59. Parish, T.,, B. G. Gordhan,, R. A. McAdam,, K. Duncan,, V. Mizrahi,, and N. G. Stoker. 1999. Production of mutants in amino acid biosynthesis genes of Mycobacterium tuberculosis by homologous recombination. Microbiology 145: 3497 3503.
60. Pavelka, M. S., Jr.,, and W. R. Jacobs, Jr. 1999. Comparison of the construction of unmarked deletion mutations in Mycobacterium smegmatis, Mycobacterium bovis bacillus Calmette- Guérin, and Mycobacterium tuberculosis H37Rv by allelic exchange. J. Bacteriol. 181: 4780 4789.
61. Primm, T.,, S. Andersen,, V. Mizrahi,, D. Avarbock,, H. Rubin,, and C. E. Barry III. 2000. The stringent response of Mycobacterium tuberculosis is required for long-term survival. J. Bacteriol. 182: 4889 4898.
62. Rad, M. E.,, P. Bifani,, C. Martin,, K. Kremer,, S. Samper,, J. Rauzier,, B. Kreiswirth,, J. Blazquez,, M. Jouan,, D. van Soolingen,, and B. Gicquel. 2003. Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family. Emerg. Infect. Dis. 9: 838 845.
63. Ramakrishnan, L.,, N. A. Federspiel,, and S. Falkow. 2000. Granuloma-specific expression of Mycobacterium virulence proteins from the glycine-rich PE-PGRS family. Science 288: 1436 1439.
64. Rand, L.,, J. Hinds,, B. Springer,, P. Sander,, R. S. Buxton,, and E. O. Davis. 2003. The majority of inducible DNA repair genes in Mycobacterium tuberculosis are induced independently of RecA. Mol. Microbiol. 50: 1031 1042.
65. Rayssiguier, C.,, D. S. Thaler,, and M. Radman. 1989. The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature 342: 396 401.
66. Reddy, M. S.,, N. Guhan,, and K. Muniyappa. 2001. Characterization of single-stranded DNA-binding proteins from mycobacteria. The carboxy-terminal domain of SSB is essential for stable association with its cognate RecA protein. J. Biol. Chem. 276: 45959 45968.
67. Richardson, A. R.,, Z. Yu,, T. Popovic,, and I. Stojiljkovic. 2002. Mutator clones of Neisseria meningitidis in epidemic serogroup A disease. Proc. Natl. Acad. Sci. USA 99: 6103 6107.
68. Sander, P.,, K. G. Papavinasasundaram,, T. Dick,, E. Stavropolous,, K. Ellrott,, B. Springer,, M. J. Colston,, and E. C. Böttger. 2001. Mycobacterium bovis BCG recA deletion mutant shows increased susceptibility to DNA-damaging agents but wild-type survival in a mouse infection model. Infect. Immun. 69: 3562 3568.
69. Sander, P.,, E. C. Böttger,, B. Springer,, B. Steinmann,, M. Rezwan,, E. Stavropoulos,, and M. J. Colston. 2003. A recA deletion mutant of Mycobacterium bovis BCG confers protection equivalent to that of wild type BCG but shows increased genetic stability. Vaccine 21: 4124 4127.
70. Sassetti, C. M.,, and E. J. Rubin. 2003. Genetic requirements for mycobacterial survival during infection . Proc. Natl. Acad. Sci. USA 100: 12989 12994.
71. Savacool, H. K.,, and R. L. Switzer. 2002. Characterization of the interaction of Bacillus subtilis PyrR with pyr mRNA by site-directed mutagenesis of the protein . J. Bacteriol. 184: 2521 2528.
72. Shankar, S.,, C. D. Hershberger,, and A. M. Chakrabarty. 1997. The nucleoside diphosphate kinase of Mycobacterium smegmatis: identification of proteins that modulate specificity of nucleoside triphosphate synthesis by the enzyme. Mol. Microbiol. 24: 477 487.
73. Sherman, D. R.,, M. Voskuil,, D. Schnappinger,, R. Liao,, M.I. Harrell,, and G.K. Schoolnik. 2001. Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding alphacrystallin. Proc. Natl. Acad. Sci. USA 98: 7534 7539.
74. Shi, W.,, L. A. Basso,, D. S. Santos,, P. C. Tyler,, R. H. Furneaux,, J. S. Blanchard,, S. C. Almo,, and V. L. Schramm. 2001. Structures of purine nucleoside phosphorylase from Mycobacterium tuberculosis in complexes with immucillin-H and its pieces. Biochemistry 40: 8204 8215.
75. Spek, E. J.,, T. L. Wright,, M. S. Stitt,, N. R. Taghizadeh,, S. R. Tannenbaum,, M. G. Marinus,, and B. P. Engelward. 2001. Recombinational repair is critical for survival of Escherichia coli exposed to nitric oxide . J. Bacteriol. 183: 131 138.
76. Sreevatsan, S.,, X. Pan,, K. E. Stockbauer,, N. D. Connell,, B. N. Kreiswirth,, T. S. Whittam,, and J. M. Musser. 1997. Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionary recent global dissemination. Proc. Natl. Acad. Sci. USA 94: 9869 9974.
77. Taylor, C. M.,, M. Beresford,, H. A. Epton,, D. C. Sigee,, G. Shama,, P. W. Andrew,, and I. S. Roberts. 2002. Listeria mono-cytogenes relA and hpt mutants are impaired in surfaceattached growth and virulence. J. Bacteriol. 184: 621 628.
78. Tsolaki, A. G.,, A. E. Hirsh,, K. DeRiemer,, J. A. Enciso,, M. Z. Wong,, M. Hannan,, Y. O. Goguet de la Salmoniere,, K. Aman,, M. Kaeto-Maeda,, and P. M. Small. 2004. Functional and evolutionary genomics of Mycobacterium tuberculosis: insights from genomic deletions in 100 strains. Proc. Natl. Acad. Sci. USA 101: 4865 4870.
79. Turner, R. J.,, E. R. Bonner,, G. K. Grabner,, and R. L. Switzer. 1998. Purification and characterization of Bacillus subtilis PyrR, a bifunctional pyr mRNA-binding attenuation protein/uracil phosphoribosyl-transferase. J. Biol. Chem. 273: 5932 5938.
80. Vaze, M. B.,, and K. Muniyappa. 1999. RecA protein of Mycobacterium tuberculosis possesses pH dependent homologous DNA pairing and strand-exchange activities: implications for allele exchange in mycobacteria. Biochemistry 38: 3175 3186.
81. Venkatesh, R.,, N. Ganesh,, N. Guhan,, M. S. Reddy,, T. Chandrasekhar,, and K. Muniyappa. 2002. RecX protein abrogates ATP hydrolysis and strand exchange promoted by RecA: insights into negative regulation of homologous recombination. Proc. Natl. Acad. Sci. USA 99: 12091 12096.
82. Venkatesh,, J. P. Kumar ,, P. S. Krishna,, R. Majunath,, and U. Varshney. 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.
83. Voskuil, M. I.,, D. Schnappinger,, K. C. Visconti,, M. I. Harrell,, G. M. Dolganov,, D. R. Sherman,, and G. K. Schoolnik. 2003. Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program . J. Exp. Med. 198: 705 713.
84. Warren, R. M.,, S. L. Sampson,, M. Richardson,, G. D. van der Spuy,, C. J. Lombard,, T. C. Victor,, and P. D. van Helden. 2000. Mapping of IS6110 flanking regions in clinical isolates of Mycobacterium tuberculosis demonstrates genome plasticity. Mol. Microbiol. 37: 1405 1416.
85. Weller, G. R.,, B. Kysela,, R. Roy,, L. M. Tonkin,, E. Scanlan,, M. Della,, S. K. Devine,, J. P. Day,, A. Wilkinson,, F. di Fagagna,, K. M. Devine,, R. P. Bowater,, P. A. Jeggo,, S. P. Jackson,, and A. J. Doherty. 2002. Identification of a DNA nonhomologous end-joining complex in bacteria. Science 297: 1686 1688.
86. Werngren, J.,, and S. E. Hoffner. 2003. Drug-susceptible Mycobacterium tuberculosis Beijing genotype does not develop mutation-conferred resistance to rifampin at an elevated rate. J. Clin. Microbiol. 41: 1520 1524.
87. Wheeler, P. R. 1987. Enzymes for purine synthesis and scavenging in pathogenic mycobacteria and their distribution in Mycobactrium leprae. J. Gen. Microbiol. 133: 3013 3018.
88. Wheeler, P. R. 1987. Biosynthesis and scavenging of purines by pathogenic mycobacteria including Mycobacterium leprae. J. Gen. Microbiol. 133: 2999 3011.
89. Wheeler, P. R. 1989. Pyrimidine biosynthesis de novo in M. leprae. FEMS Microbiol. Lett. 48: 185 189.
90. Wheeler, P. R. 1990. Biosynthesis and scavenging of pyrimidines by pathogenic mycobacteria. J. Gen. Microbiol. 136: 189 201.
91. Yang, F.,, S. C. Curran,, L. S. Li,, D. Avarbock,, J. D. Graf,, M. M. Chua,, G. Lu,, J. Salem,, and H. Rubin. 1997. Characterization of two genes encoding the Mycobacterium tuberculosis ribonucleotide reductase small subunit. J. Bacteriol. 179: 6408 6415.
92. Yang, F.,, G. Lu,, and H. Rubin. 1994. Isolation of ribonucleotide reductase from Mycobacterium tuberculosis and cloning, expression and purification of the large subunit . J. Bacteriol. 176: 6738 6743.
93. Yeiser, B.,, E. D. Pepper,, M. F. Goodman,, and S. E. Finkel. 2002. SOS-induced DNA polymerases enhance long-term survival and evolutionary fitness. Proc. Natl. Acad. Sci. USA 99: 8737 8741.
94. Zaborina, O.,, X. Li,, G. Cheng,, V. Kapatral,, and A. M. Chakrabarty. 1999. Secretion of ATP-utilizing enzymes, nucleoside diphosphate kinase and ATPase, by Mycobacterium bovis BCG: sequestration of ATP from macrophage P2Z receptors? Mol. Microbiol. 5: 1333 1343.
95. Zhang, Y.,, and A. Telenti,. 2000. Genetics of drug resistance in M. tuberculosis, p. 235 254. In G. F. Hatfull, and W. R. Jacobs, Jr. (ed.), Molecular Genetics of Mycobacteria. ASM Press, Washington, D.C.


Generic image for table
Table 1

Mechanisms underlying genome plasticity in

Citation: Mizrahi V, Buckstein M, Rubin H. 2005. Nucleic Acid Metabolism, p 369-378. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch23

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error