1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Hairpin Telomere Resolvases

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • HTML
    136.27 Kb
  • PDF
    750.83 Kb
  • XML
    100.75 Kb
  • Authors: Kerri Kobryn1, George Chaconas2
  • Editors: Phoebe Rice3, Nancy Craig4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada; 2: Department of Biochemistry & Molecular Biology and Department of Microbiology, Immunology & Infectious Diseases, Snyder Institute, The University of Calgary, Calgary, AB T2N 4N1, Canada; 3: University of Chicago, Chicago, IL; 4: Johns Hopkins University, Baltimore, MD
  • Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.MDNA3-0023-2014
  • Received 07 July 2014 Accepted 08 July 2014 Published 21 November 2014
  • George Chaconas, chaconas@ucalgary.ca
image of Hairpin Telomere Resolvases
    Preview this microbiology spectrum article:
    Zoom in
    Zoomout

    Hairpin Telomere Resolvases, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/2/6/MDNA3-0023-2014-1.gif /docserver/preview/fulltext/microbiolspec/2/6/MDNA3-0023-2014-2.gif
  • Abstract:

    Covalently closed hairpin ends, also known as hairpin telomeres, provide an unusual solution to the end replication problem. The hairpin telomeres are generated from replication intermediates by a process known as telomere resolution. This is a DNA breakage and reunion reaction promoted by hairpin telomere resolvases (also referred to as protelomerases) found in a limited number of phage and bacteria. The reaction promoted by these enzymes is a chemically isoenergetic two-step transesterification without a requirement for divalent metal ions or high-energy cofactors and uses an active site and mechanism similar to that for type IB topoisomerases and tyrosine recombinases. The small number of unrelated telomere resolvases characterized to date all contain a central, catalytic core domain with the active site, but in addition carry variable C- and N-terminal domains with different functions. Similarities and differences in the structure and function of the telomere resolvases are discussed. Of particular interest are the properties of the telomere resolvases, which have been studied most extensively at the biochemical level and appear to play a role in shaping the unusual segmented genomes in these organisms and, perhaps, to play a role in recombinational events.

  • Citation: Kobryn K, Chaconas G. 2014. Hairpin Telomere Resolvases. Microbiol Spectrum 2(6):MDNA3-0023-2014. doi:10.1128/microbiolspec.MDNA3-0023-2014.

Key Concept Ranking

DNA Synthesis
0.48054084
Hairpin Telomeres
0.47043002
Type IB Topoisomerase
0.44924498
Cellular Processes
0.4214138
0.48054084

References

1. Chaconas G. 2005. Hairpin telomeres and genome plasticity in Borrelia: all mixed up in the end. Mol Microbiol 58:625–635. [PubMed][CrossRef]
2. Chaconas G, Kobryn K. 2010. Structure, function, and evolution of linear replicons in Borrelia. Annu Rev Microbiol 64:185–202. [PubMed][CrossRef]
3. Deneke J, Ziegelin G, Lurz R, Lanka E. 2000. The protelomerase of temperate Escherichia coli phage N15 has cleaving-joining activity. Proc Natl Acad Sci U S A 97:7721–7726. [PubMed][CrossRef]
4. Huang WM, Joss L, Hsieh T, Casjens S. 2004. Protelomerase uses a topoisomerase IB/Y-recombinase type mechanism to generate DNA hairpin ends. J Mol Biol 337:77–92. [PubMed][CrossRef]
5. Hertwig S, Klein I, Lurz R, Lanka E, Appel B. 2003. PY54, a linear plasmid prophage of Yersinia enterocolitica with covalently closed ends. Mol Microbiol 48:989–1003. [PubMed][CrossRef]
6. Kobryn K, Chaconas G. 2002. ResT, a telomere resolvase encoded by the Lyme disease spirochete. Mol Cell 9:195–201. [PubMed][CrossRef]
7. Moriarty TJ, Chaconas G. 2009. Identification of the determinant conferring permissive substrate usage in the telomere resolvase, ResT. J Biol Chem 284:23293–23301. [PubMed][CrossRef]
8. Huang WM, DaGloria J, Fox H, Ruan Q, Tillou J, Shi K, Aihara H, Aron J, Casjens S. 2012. Linear chromosome-generating system of Agrobacterium tumefaciens C58: protelomerase generates and protects hairpin ends. J Biol Chem 287:25551–25563. [PubMed][CrossRef]
9. Ramirez-Bahena MH, Vial L, Lassalle F, Diel B, Chapulliot D, Daubin V, Nesme X, Muller D. 2014. Single acquisition of protelomerase gave rise to speciation of a large and diverse clade within the Agrobacterium/Rhizobium supercluster characterized by the presence of a linear chromid. Mol Phylogenet Evol 73: 202–207. [PubMed][CrossRef]
10. Chaconas G, Stewart PE, Tilly K, Bono JL, Rosa P. 2001. Telomere resolution in the Lyme disease spirochete. EMBO J 20:3229–3237. [PubMed][CrossRef]
11. Tourand Y, Kobryn K, Chaconas G. 2003. Sequence-specific recognition but position-dependent cleavage of two distinct telomeres by the Borrelia burgdorferi telomere resolvase, ResT. Mol Microbiol 48:901–911. [PubMed][CrossRef]
12. Bankhead T, Chaconas G. 2004. Mixing active site components: A recipe for the unique enzymatic activity of a telomere resolvase. Proc Natl Acad Sci U S A 101:13768–13773. [PubMed][CrossRef]
13. Deneke J, Burgin AB, Wilson SL, Chaconas G. 2004. Catalytic residues of the telomere resolvase ResT: a pattern similar to, but distinct from tyrosine recombinases and type IB topoisomerases. J Biol Chem 279:53699–53706. [PubMed][CrossRef]
14. Kobryn K, Burgin AB, Chaconas G. 2005. Uncoupling the chemical steps of telomere resolution by ResT. J Biol Chem 280:26788–26795. [PubMed][CrossRef]
15. Kobryn K, Chaconas G. 2005. Fusion of hairpin telomeres by the B. burgdorferi telomere resolvase ResT: Implications for shaping a genome in flux. Mol Cell 17:783–791. [PubMed][CrossRef]
16. Bankhead T, Kobryn K, Chaconas G. 2006. Unexpected twist: harnessing the energy in positive supercoils to control telomere resolution. Mol Microbiol 62:895–905. [PubMed][CrossRef]
17. Tourand Y, Bankhead T, Wilson SL, Putteet-Driver AD, Barbour AG, Byram R, Rosa PA, Chaconas G. 2006. Differential telomere processing by Borrelia telomere resolvases in vitro but not in vivo. J Bacteriol 188:7378–7386. [PubMed][CrossRef]
18. Tourand Y, Lee L, Chaconas G. 2007. Telomere resolution by Borrelia burgdorferi ResT through the collaborative efforts of tethered DNA binding domains. Mol Microbiol 64:580–590. [PubMed][CrossRef]
19. Lefas G, Chaconas G. 2009. High-throughput screening identifies three inhibitor classes of the telomere resolvase from the Lyme disease spirochete. Antimicrob Agents Chemother 53:4441–4449. [PubMed][CrossRef]
20. Tourand Y, Deneke J, Moriarty TJ, Chaconas G. 2009. Characterization and in vitro reaction properties of 19 unique hairpin telomeres from the linear plasmids of the Lyme disease spirochete. J Biol Chem 284:7264–7272. [PubMed][CrossRef]
21. Kobryn K, Briffotaux J, Karpov V. 2009. Holliday junction formation by the Borrelia burgdorferi telomere resolvase, ResT: implications for the origin of genome linearity. Mol Microbiol 71:1117–1130. [PubMed][CrossRef]
22. Briffotaux J, Kobryn K. 2010. Preventing broken borrelia telomeres: Rest couples dual hairpin telomere formation to product release. J Biol Chem 285: 41010–41018. [PubMed][CrossRef]
23. Mir T, Huang SH, Kobryn K. 2013. The telomere resolvase of the Lyme disease spirochete, Borrelia burgdorferi, promotes DNA single-strand annealing and strand exchange. Nucleic Acids Res 41:10438–10448. [PubMed][CrossRef]
24. Deneke J, Ziegelin G, Lurz R, Lanka E. 2002. Phage N15 telomere resolution: Target requirements for recognition and processing by the protelomerase. J Biol Chem 277:10410–10419. [PubMed][CrossRef]
25. Aihara H, Huang WM, Ellenberger T. 2007. An interlocked dimer of the protelomerase TelK distorts DNA structure for the formation of hairpin telomeres. Mol Cell 27:901–913. [PubMed][CrossRef]
26. Shi K, Huang WM, Aihara H. 2013. An enzyme-catalyzed multistep DNA refolding mechanism in hairpin telomere formation. PLoS Biol 11:e1001472. [PubMed][CrossRef]
27. Shuman S. 1998. Vaccinia virus DNA topoisomerase: a model eukaryotic type IB enzyme. Biochim Biophys Acta 1400:321–337. [PubMed][CrossRef]
28. Van Duyne GD. 2002. A structural view of tyrosine recombinase site-specific recombination, p 93–117. In Craig NL, Craigie R, Gellert M, Lambowitz AM (ed), Mobile DNA II. ASM Press, Washington, DC.
29. Grindley ND, Whiteson KL, Rice PA. 2006. Mechanisms of site-specific recombination. Annu Rev Biochem 75:567–605. [PubMed][CrossRef]
30. Lee J, Tonozuka T, Jayaram M. 1997. Mechanism of active site exclusion in a site-specific recombinase: role of the DNA substrate in conferring half-of-the-sites activity. Genes Dev 11:3061–3071. [PubMed][CrossRef]
31. Voziyanov Y, Pathania S, Jayaram M. 1999. A general model for site-specific recombination by the integrase family recombinases. Nucleic Acids Res 27:930–941. [PubMed][CrossRef]
32. Conway AB, Chen Y, Rice PA. 2003. Structural plasticity of the Flp-Holliday junction complex. J Mol Biol 326:425–434. [PubMed][CrossRef]
33. Burgin AB, Jr, Nash HA. 1995. Suicide substrates reveal properties of the homology-dependent steps during integrative recombination of bacteriophage lambda. Curr Biol 5:1312–1321. [PubMed][CrossRef]
34. Barre FX, Aroyo M, Colloms SD, Helfrich A, Cornet F, Sherratt DJ. 2000. FtsK functions in the processing of a Holliday junction intermediate during bacterial chromosome segregation. Genes Dev 14:2976–2988. [PubMed][CrossRef]
35. Rybchin VN, Svarchevsky AN. 1999. The plasmid prophage N15: a linear DNA with covalently closed ends. Mol Microbiol 33:895–903. [PubMed][CrossRef]
36. Krogh BO, Shuman S. 2000. Catalytic mechanism of DNA topoisomerase IB. Mol Cell 5:1035–1041. [PubMed][CrossRef]
37. Krogh BO, Shuman S. 2002. Proton relay mechanism of general acid catalysis by DNA topoisomerase IB. J Biol Chem 277:5711–5714. [PubMed][CrossRef]
38. Burgin AB. 2001. Synthesis and use of DNA containing a 5′-bridging phosphorothioate as a suicide substrate for type I DNA topoisomerases. Methods Mol Biol 95:119–128. [PubMed]
39. Van Duyne GD. 2001. A structural view of cre-loxp site-specific recombination. Annu Rev Biophys Biomol Struct 30:87–104. [PubMed][CrossRef]
40. Chen Y, Rice PA. 2003. The role of the conserved Trp330 in Flp-mediated recombination. Functional and structural analysis. J Biol Chem 278:24800–24807. [PubMed][CrossRef]
41. Whiteson KL, Chen Y, Chopra N, Raymond AC, Rice PA. 2007. Identification of a potential general acid/base in the reversible phosphoryl transfer reactions catalyzed by tyrosine recombinases: Flp H305. Chem Biol 14:121–129. [PubMed][CrossRef]
42. Davies DR, Mushtaq A, Interthal H, Champoux JJ, Hol WG. 2006. The structure of the transition state of the heterodimeric topoisomerase I of Leishmania donovani as a vanadate complex with nicked DNA. J Mol Biol 357:1202–1210. [PubMed][CrossRef]
43. Kobryn K. 2007. The linear hairpin replicons of Borrelia burgdorferi, p 117–140. In Meinhardt F, Klassen R (ed), Microbial Linear Plasmids. Springer, Berlin Heidelberg. [CrossRef]
44. Casjens S, Palmer N, van Vugt R, Huang WH, Stevenson B, Rosa P, Lathigra R, Sutton G, Peterson J, Dodson RJ, Haft D, Hickey E, Gwinn M, White O, Fraser CM. 2000. A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi. Mol Microbiol 35:490–516. [PubMed][CrossRef]
45. Fraser CM, Casjens S, Huang WM, Sutton GG, Clayton R, Lathigra R, White O, Ketchum KA, Dodson R, Hickey EK, Gwinn M, Dougherty B, Tomb JF, Fleischmann RD, Richardson D, Peterson J, Kerlavage AR, Quackenbush J, Salzberg S, Hanson M, van Vugt R, Palmer N, Adams MD, Gocayne J, Weidman J, Utterback T, Watthey L, McDonald L, Artiach P, Bowman C, Garland S, Fujii C, Cotton MD, Horst K, Roberts K, Hatch B, Smith HO, Venter JC. 1997. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390:580–586. [PubMed][CrossRef]
46. Casjens SR, Mongodin EF, Qiu WG, Luft BJ, Schutzer SE, Gilcrease EB, Huang WM, Vujadinovic M, Aron JK, Vargas LC, Freeman S, Radune D, Weidman JF, Dimitrov GI, Khouri HM, Sosa JE, Halpin RA, Dunn JJ, Fraser CM. 2012. Genome stability of Lyme disease spirochetes: comparative genomics of Borrelia burgdorferi plasmids. PloS One 7:e33280. [PubMed][CrossRef]
47. Huang WM, Robertson M, Aron J, Casjens S. 2004. Telomere exchange between linear replicons of Borrelia burgdorferi. J Bacteriol 186:4134–4141. [PubMed][CrossRef]
48. Casjens S, Murphy M, DeLange M, Sampson L, van Vugt R, Huang WM. 1997. Telomeres of the linear chromosomes of Lyme disease spirochaetes: nucleotide sequence and possible exchange with linear plasmid telomeres. Mol Microbiol 26:581–596. [PubMed][CrossRef]
49. Terekhova D, Iyer R, Wormser GP, Schwartz I. 2006. Comparative genome hybridization reveals substantial variation among clinical isolates of Borrelia burgdorferi sensu stricto with different pathogenic properties. J Bacteriol 188:6124–6134. [PubMed][CrossRef]
50. Davies DR, Goryshin IY, Reznikoff WS, Rayment I. 2000. Three-dimensional structure of the Tn5 synaptic complex transposition intermediate. Science 289:77–85. [PubMed][CrossRef]
51. Lovell S, Goryshin IY, Reznikoff WR, Rayment I. 2002. Two-metal active site binding of a Tn5 transposase synaptic complex. Nat Struct Biol 9:278–281. [PubMed][CrossRef]
52. Ason B, Reznikoff WS. 2002. Mutational analysis of the base flipping event found in Tn5 transposition. J Biol Chem 277:11284–11291. [PubMed][CrossRef]
53. Allingham JS, Wardle SJ, Haniford DB. 2001. Determinants for hairpin formation in Tn10 transposition. EMBO J 20:2931–2942. [PubMed][CrossRef]
54. Bischerour J, Chalmers R. 2007. Base-flipping dynamics in a DNA hairpin processing reaction. Nucleic Acids Res 35:2584–2595. [PubMed][CrossRef]
55. Bischerour J, Chalmers R. 2009. Base flipping in tn10 transposition: an active flip and capture mechanism. PloS One 4:e6201. [PubMed][CrossRef]
56. Ghosh K, Lau CK, Gupta K, Van Duyne GD. 2005. Preferential synapsis of loxP sites drives ordered strand exchange in Cre-loxP site-specific recombination. Nat Chem Biol 1:275–282. [PubMed][CrossRef]
57. Hoess RH, Wierzbicki A, Abremski K. 1986. The role of the loxP spacer region in P1 site-specific recombination. Nucleic Acids Res 14:2287–2300. [PubMed][CrossRef]
58. Lee L, Chu LC, Sadowski PD. 2003. Cre induces an asymmetric DNA bend in its target loxP site. J Biol Chem 278:23118–23129. [PubMed][CrossRef]
59. Lee L, Sadowski PD. 2003. Sequence of the loxP site determines the order of strand exchange by the Cre recombinase. J Mol Biol 326:397–412. [PubMed][CrossRef]
60. Senecoff JF, Cox MM. 1986. Directionality in FLP protein-promoted site-specific recombination is mediated by DNA-DNA pairing. J Biol Chem 261:7380–7386. [PubMed]
61. Cui T, Moro-oka N, Ohsumi K, Kodama K, Ohshima T, Ogasawara N, Mori H, Wanner B, Niki H, Horiuchi T. 2007. Escherichia coli with a linear genome. EMBO Rep 8:181–187. [PubMed][CrossRef]
62. Aussel L, Barre FX, Aroyo M, Stasiak A, Stasiak AZ, Sherratt D. 2002. FtsK Is a DNA motor protein that activates chromosome dimer resolution by switching the catalytic state of the XerC and XerD recombinases. Cell 108:195–205. [PubMed][CrossRef]
63. Bigot S, Saleh OA, Lesterlin C, Pages C, El Karoui M, Dennis C, Grigoriev M, Allemand JF, Barre FX, Cornet F. 2005. KOPS: DNA motifs that control E. coli chromosome segregation by orienting the FtsK translocase. EMBO J 24:3770–3780. [PubMed][CrossRef]
64. Kuzminov A. 1999. Recombinational repair of DNA damage in Escherichia coli and bacteriophage lambda. Microbiol Mol Biol Rev 63:751–813. [PubMed]
65. Coutte L, Botkin DJ, Gao L, Norris SJ. 2009. Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of Borrelia burgdorferi infection. PLoS Pathog 5:e1000293. [PubMed][CrossRef]
66. Dresser AR, Hardy P-O, Chaconas G. 2009. Investigation of the role of DNA replication, recombination and repair genes in antigenic switching at the vlsE locus in Borrelia burgdorferi: an essential role for the RuvAB branch migrase. PLoS Pathog 5:e1000680. [PubMed][CrossRef]
67. Lin T, Gao L, Edmondson DG, Jacobs MB, Philipp MT, Norris SJ. 2009. Central role of the Holliday junction helicase RuvAB in vlsE recombination and infectivity of Borrelia burgdorferi. PLoS Pathog 12:e1000679. [PubMed][CrossRef]
68. Byram R, Stewart PE, Rosa P. 2004. The essential nature of the ubiquitous 26-kilobase circular replicon of Borrelia burgdorferi. J Bacteriol 186:3561–3569. [PubMed][CrossRef]
69. Bandy NJ, Salman-Dilgimen A, Chaconas G. 2014. Construction and characterization of a B. burgdorferi strain with conditional expression of the essential telomere resolvase, ResT. Journal of Bacteriology 196:2396–2404. [PubMed][CrossRef]
70. Hinnebusch J, Barbour AG. 1991. Linear plasmids of Borrelia burgdorferi have a telomeric structure and sequence similar to those of a eukaryotic virus. J Bacteriol 173:7233–7239. [PubMed]
71. Hinnebusch J, Bergstrom S, Barbour AG. 1990. Cloning and sequence analysis of linear plasmid telomeres of the bacterium Borrelia burgdorferi. Mol Microbiol 4:811–820. [PubMed][CrossRef]
72. Zhang JR, Hardham JM, Barbour AG, Norris SJ. 1997. Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes. Cell 89:275–285. [PubMed][CrossRef]
73. Froelich-Ammon SJ, Osheroff N. 1995. Topoisomerase poisons: harnessing the dark side of enzyme mechanism. J Biol Chem 270:21429–21432. [PubMed][CrossRef]
74. Pinder DJ, Blake CE, Lindsey JC, Leach DR. 1998. Replication strand preference for deletions associated with DNA palindromes. Mol Microbiol 28:719–727. [PubMed][CrossRef]
75. Leach DR, Okely EA, Pinder DJ. 1997. Repair by recombination of DNA containing a palindromic sequence. Mol Microbiol 26:597–606. [PubMed][CrossRef]
microbiolspec.MDNA3-0023-2014.citations
cm/2/6
content/journal/microbiolspec/10.1128/microbiolspec.MDNA3-0023-2014
Loading

Citations loading...

Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.MDNA3-0023-2014
2014-11-21
2017-11-19

Abstract:

Covalently closed hairpin ends, also known as hairpin telomeres, provide an unusual solution to the end replication problem. The hairpin telomeres are generated from replication intermediates by a process known as telomere resolution. This is a DNA breakage and reunion reaction promoted by hairpin telomere resolvases (also referred to as protelomerases) found in a limited number of phage and bacteria. The reaction promoted by these enzymes is a chemically isoenergetic two-step transesterification without a requirement for divalent metal ions or high-energy cofactors and uses an active site and mechanism similar to that for type IB topoisomerases and tyrosine recombinases. The small number of unrelated telomere resolvases characterized to date all contain a central, catalytic core domain with the active site, but in addition carry variable C- and N-terminal domains with different functions. Similarities and differences in the structure and function of the telomere resolvases are discussed. Of particular interest are the properties of the telomere resolvases, which have been studied most extensively at the biochemical level and appear to play a role in shaping the unusual segmented genomes in these organisms and, perhaps, to play a role in recombinational events.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

/deliver/fulltext/microbiolspec/2/6/MDNA3-0023-2014.html?itemId=/content/journal/microbiolspec/10.1128/microbiolspec.MDNA3-0023-2014&mimeType=html&fmt=ahah

Figures

Image of FIGURE 1

Click to view

FIGURE 1

Hairpin telomere resolution as a solution to the end replication problem. Replication of a linear molecule results in the formation of dimer junctions or replicated telomeres (L′L, RR′) that are processed by telomere resolution, a unique type of DNA breakage and reunion reaction. Telomere resolution results in the formation of hairpin telomeres at the ends of the linear DNA molecule and separates the dimer replication intermediate into monomeric products of DNA replication. See text for further details. This figure is adapted from reference 6 and reprinted from reference 1 . doi:10.1128/microbiolspec.MDNA3-0023-2014.f1

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.MDNA3-0023-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Click to view

FIGURE 2

ResT promotes telomere resolution via a two-step transesterification. (1) The telomere resolvase, ResT, binds to a replicated telomere () substrate, which corresponds to the dimer junction L′L or RR′ shown in Fig. 1 ( 11 ). The black dots denote the scissile phosphates and the vertical bar in the center of the axis of 180-degree rotational symmetry. (2) Positive supercoiling is believed to facilitate the cooperative formation of a cross-axis complex where communication between ResT protomers bound on both sides of the symmetry axis occurs ( 14 , 16 ). (3) The action of the “hairpin binding module,” a region with sequence similarity to a motif found in cut-and-paste transposases, induces a DNA distortion that facilitates (4) DNA cleavage, the first transesterification event ( 12 ). (5) A conformational change then occurs to juxtapose the free 5′-OH groups to the 3-phosphotyrosyl enzyme intermediates on the opposite strands. (6) Nucleophilic attack of the phosphotyrosyl linkage by the 5′-OH groups, the second transesterification step, results in phosphodiester bond formation to stabilize the hairpins generated during step 5. This figure and legend are adapted from reference 43 and reference 21 , and reprinted from reference 2 . doi:10.1128/microbiolspec.MDNA3-0023-2014.f2

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.MDNA3-0023-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Click to view

FIGURE 3

Sequence alignment of the domains carrying the active site residues of purified telomere resolvases. An alignment is shown for the telomere resolvases from the phages N15, TelN ( 3 ), ɸKO2, TelK ( 4 ), PY54, TelY ( 5 ) and the bacterial resolvases from TelA ( 8 ), the Lyme spirochete ResTBb ( 6 ) and the relapsing fever species ResTBh ( 7 ). Several other purified hairpin resolvases from other species are not included in the lineup. The catalytic residues are indicated by asterisks and the active site tyrosine by a red asterisk. The double colon indicates the position of the proline in ResT that confers permissiveness for Type 2 telomeres ( 7 ). The corresponding active site residues for the tyrosine recombinase family are indicated above and below the alignment in red and those for type IB topoisomerases in blue. doi:10.1128/microbiolspec.MDNA3-0023-2014.f3

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.MDNA3-0023-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

Click to view

FIGURE 4

telomere sequence alignment. Telomere sequences are arranged in descending order, according to the initial rate of telomere resolution. The initial rate, expressed in fmol/min is shown in the right-hand column and telomere sequences are aligned with the hairpins (or symmetry axis in the replicated telomeres) at the left end. The telomeres shown are half of the actual replicated telomere substrates used in the telomere resolution reactions. The colored boxes labeled 1 and 3 refer to previously identified regions of sequence homology ( 11 ), with some modifications. The original box 1 sequence, TATAAT is indicated by a light blue box, while the newly identified box 1 sequence, TATTAT is shown in dark blue. The homology box 3 region has been expanded from the five nucleotide sequence TAGTA to the eight nucleotide sequence TTAGTATA. The telomere sequences of lp17L, lp17R, lp21R, lp28-1R, lp56R ChromL and ChromR have been reported previously ( 45 , 47 , 48 , 70 , 71 , 72 ). Reprinted from reference 20 . doi:10.1128/microbiolspec.MDNA3-0023-2014.f4

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.MDNA3-0023-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5

Click to view

FIGURE 5

Telomere exchanges believed to be mediated by ResT promoted telomere fusions. The proposed mechanism for telomere exchange between linear plasmids and the right end of the chromosome is a two-step process. The first is a telomere fusion event and the second is a deletion or other type of mutation to inactivate or remove the newly fused telomere and prevent its resolution and to remove competing replication maintenance functions. The telomere fusion event is promoted by reversal of the ResT reaction such that two hairpin telomeres from different molecules are fused to generate a single DNA molecule carrying a replicated telomere. A deletion removing the telomere resolution site might be specifically targeted to the fused telomere by incomplete joining in the reverse reaction, to leave a ResT molecule covalently linked at a nick in the telomere; such covalent protein–DNA complexes are known to be foci for the formation of deletions and other chromosomal aberrations ( 73 ). Alternatively, a deletion could be derived from palindrome instability induced by passage of a replication fork through the inverted repeat of the fused telomere ( 74 , 75 ). chromosome extensions that may have arisen by ResT-mediated telomere fusions followed by deletion formation (see references 1 , 2 , 15 ). The B31 chromosome appears to have arisen from fusion of an lp28-1 plasmid with the N40 chromosome. Subsequently, a single fusion of the B31 chromosome with lp21, followed by sequence deletion would have generated the 297 chromosome. Similarly, two rounds of fusion/deletion of the B31 chromosome, first with an lp28-1 and subsequently with lp28-5, would have generated the JD1 chromosome. The sequence relatedness of the chromosomes and plasmids shown were reported by references 44 , 46 , 47 , 48 . This figure is slightly modified from reference 46 . doi:10.1128/microbiolspec.MDNA3-0023-2014.f5

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.MDNA3-0023-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 6

Click to view

FIGURE 6

The domain structure of hairpin telomere resolvases. The domain composition of the telomere resolvases from phage ɸKO2 (TelK), (TelA) and species (ResT) are shown (see also text). All telomere resolvases have a central catalytic domain with active site residues similar those of tyrosine recombinases and type IB topoisomerses (see Fig. 3 and text). In addition, hairpin resolvases carry divergent N-terminal domains; they may also carry a divergent C-terminal region or it may be absent as for TelA. Domains represented by the same shape and color scheme are structurally related. Domains delimited by brackets represent protein sequences dispensable for telomere resolution ( 8 , 25 ). Also shown for each hairpin telomere resolvase is the tyrosine nucleophile (Y). The numbers above the graphics refer to the amino acid numbers of the proteins. Precise domain boundaries have been adjusted from those previously reported based upon structural alignments. and A structural view of the domain organization of TelK and TelA, respectively. The domains are represented by the same color scheme used in on one monomer in each dimer. The N-core domain, represented in blue, is composed of a helical bundle that forms the top of the C-clamp embrace the resolvases make with the substrate DNA and the long linker α-helix that connects the top and bottom of the C-clamp. TelK has a large insertion in the N-core domain called the muzzle; this is represented in yellow. The shared catalytic domain is represented in red. TelK has an additional C-terminal domain essential for telomere resolution called the stirrup; this domain is represented in grey. Beyond the shared catalytic domain TelA lacks an additional domain like the stirrup but instead has a short segment that contributes to dimerization contacts; this short C-terminal extension is represented in green. The arrows with residue numbers indicate the position in the structure of the first and last resolvable residues present in the structures. The structures presented were generated with The PyMOL Molecular Graphics System, Version 1.7 Schrödinger, LLC. (http://www.pymol.org/) using PDB ID 2v6e for TelK ( 25 ) and 4e0g for TelA ( 26 ). doi:10.1128/microbiolspec.MDNA3-0023-2014.f6

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.MDNA3-0023-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 7

Click to view

FIGURE 7

TelK and TelA-DNA complexes showing displacement of the helical axes at the dimer interface by 7.5 and >10 angstroms, respectively. The structures presented were generated with The PyMOL Molecular Graphics System, Version 1.7 Schrödinger, LLC. (http://www.pymol.org/) using PDB ID 2v6e for TelK ( 25 ) and 4e0g for TelA ( 26 ). doi:10.1128/microbiolspec.MDNA3-0023-2014.f7

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.MDNA3-0023-2014
Permissions and Reprints Request Permissions
Download as Powerpoint

Supplemental Material

No supplementary material available for this content.

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