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.

Site-specific DNA Inversion by Serine Recombinases

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • XML
    262.59 Kb
  • HTML
    278.48 Kb
  • PDF
    1.43 MB
  • Author: Reid C. Johnson1
  • Editors: Phoebe Rice2, Nancy Craig3
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1737; 2: University of Chicago, Chicago, IL; 3: Johns Hopkins University, Baltimore, MD
  • Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
  • Received 13 June 2014 Accepted 09 October 2014 Published 19 February 2015
  • Reid Johnson, rcjohnson@mednet.ucla.edu
image of Site-specific DNA Inversion by Serine Recombinases
    Preview this microbiology spectrum article:
    Zoom in
    Zoomout

    Site-specific DNA Inversion by Serine Recombinases, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/3/1/MDNA3-0047-2014-1.gif /docserver/preview/fulltext/microbiolspec/3/1/MDNA3-0047-2014-2.gif
  • Abstract:

    Reversible site-specific DNA inversion reactions are widely distributed in bacteria and their viruses. They control a range of biological reactions that most often involve alterations of molecules on the surface of cells or phage. These programmed DNA rearrangements usually occur at a low frequency, thereby preadapting a small subset of the population to a change in environmental conditions, or in the case of phages, an expanded host range. A dedicated recombinase, sometimes with the aid of additional regulatory or DNA architectural proteins, catalyzes the inversion of DNA. RecA or other components of the general recombination-repair machinery are not involved. This chapter discusses site-specific DNA inversion reactions mediated by the serine recombinase family of enzymes and focuses on the extensively studied serine DNA invertases that are stringently controlled by the Fis-bound enhancer regulatory system. The first section summarizes biological features and general properties of inversion reactions by the Fis/enhancer-dependent serine invertases and the recently described serine DNA invertases in . Mechanistic studies of reactions catalyzed by the Hin and Gin invertases are then explored in more depth, particularly with regards to recent advances in our understanding of the function of the Fis/enhancer regulatory system. These include the steps leading to the formation of the active recombination complex (invertasome) containing the recombinase tetramer and Fis/enhancer element and the process of DNA strand exchange by rotation of synapsed subunit pairs within the invertasome. The role of DNA topological forces that function in concert with the Fis/enhancer controlling element in specifying the overwhelming bias for DNA inversion over deletion and intermolecular recombination is also discussed.

  • Citation: Johnson R. 2015. Site-specific DNA Inversion by Serine Recombinases. Microbiol Spectrum 3(1):MDNA3-0047-2014. doi:10.1128/microbiolspec.MDNA3-0047-2014.

Key Concept Ranking

Thin Layer Chromatography
0.4064074
0.4064074

References

1. Grindley ND, Whiteson KL, Rice PA. 2006. Mechanisms of site-specific recombination. Annu Rev Biochem 75:567–605. [PubMed][CrossRef]
2. Johnson RC. 2002. Bacterial site-specific DNA inversion systems, p 230–271. In Craig NL, Craigie R, Gellert M, Lambowitz AM (ed), Mobile DNA II. ASM Press, Washington DC.
3. Rice PA. Serine Resolvases. In Craig NL (ed.), Mobile DNA III. ASM Press, Washington, DC, in press.
4. Stark WM. 2014. The Serine Recombinases. Microbiolspec 2(6): doi: 10.1128/microbiolspec.MDNA3-0046-2014. [CrossRef]
5. Andrewes FW. 1922. Studies in group-agglutination - The Salmonella group and its antigenic structure. J Pathol Bacteriol 25:505–521. [CrossRef]
6. Iino T. 1969. Genetics and chemistry of bacterial flagella. Bacteriol Rev 33:454–475. [PubMed]
7. Lederberg J, Edwards P. 1953. Serotypic recombination in Salmonella. J Immunol 71:323–340. [PubMed]
8. Lederberg J, Iino T. 1956. Phase variation in Salmonella. Genetics 41:743–757. [PubMed]
9. Stocker BAD. 1949. Measurement of the rate of mutation of flagellar antigenic phase in Salmonella typhimurium. J Hyg 47:398–413. [PubMed][CrossRef]
10. Kutsukake K, Nakashima H, Tominaga A, Abo T. 2006. Two DNA invertases contribute to flagellar phase variation in Salmonella enterica serovar Typhimurium strain LT2. J Bacteriol 188:950–957. [PubMed][CrossRef]
11. Gillen KL, Hughes KT. 1991. Negative regulatory loci coupling flagellin synthesis to flagellar assembly in Salmonella typhimurium. J Bacteriol 173:2301–2310. [PubMed]
12. Ikeda JS, Schmitt CK, Darnell SC, Watson PR, Bispham J, Wallis TS, Weinstein DL, Metcalf ES, Adams P, O'Connor CD, O'Brien AD. 2001. Flagellar phase variation of Salmonella enterica serovar Typhimurium contributes to virulence in the murine typhoid infection model but does not influence Salmonella-induced enteropathogenesis. Infect Immun 69:3021–3030. [PubMed][CrossRef]
13. Zieg J, Silverman M, Hilmen M, Simon M. 1977. Recombinational switch for gene expression. Science 196:170–172. [PubMed][CrossRef]
14. Zieg J, Hilmen M, Simon M. 1978. Regulation of gene expression by site-specific inversion. Cell 15:237–244. [PubMed][CrossRef]
15. Zieg J, Simon M. 1980. Analysis of the nucleotide sequence of an invertible controlling element. Proc Natl Acad Sci U S A 77:4196–4200. [PubMed][CrossRef]
16. Silverman M, Simon M. 1980. Phase variation: genetic analysis of switching mutants. Cell 19:845–854. [PubMed][CrossRef]
17. Silverman M, Zieg J, Mandel G, Simon M. 1981. Analysis of the functional components of the phase variation system. Cold Spring Harb Symp Quant Biol 45:17–26. [PubMed][CrossRef]
18. Osuna R, Lienau D, Hughes KT, Johnson RC. 1995. Sequence, regulation, and functions of fis in Salmonella typhimurium. J Bacteriol 177:2021–2032. [PubMed]
19. Silverman M, Zieg J, Simon M. 1979. Flagellar-phase variation: isolation of the rh1 gene. J Bacteriol 137:517–523. [PubMed]
20. Aldridge PD, Wu C, Gnerer J, Karlinsey JE, Hughes KT, Sachs MS. 2006. Regulatory protein that inhibits both synthesis and use of the target protein controls flagellar phase variation in Salmonella enterica. Proc Natl Acad Sci U S A 103:11340–11345. [PubMed][CrossRef]
21. Yamamoto S, Kutsukake K. 2006. FljA-mediated posttranscriptional control of phase 1 flagellin expression in flagellar phase variation of Salmonella enterica serovar Typhimurium. J Bacteriol 188:958–967. [PubMed][CrossRef]
22. Bonifield HR, Hughes KT. 2003. Flagellar phase variation in Salmonella enterica is mediated by a posttranscriptional control mechanism. J Bacteriol 185:3567–3574. [PubMed][CrossRef]
23. Johnson RC, Bruist MF, Simon MI. 1986. Host protein requirements for in vitro site-specific DNA inversion. Cell 46:531–539. [PubMed][CrossRef]
24. Finkel SE, Johnson RC. 1992. The Fis protein: it's not just for DNA inversion anymore. Mol Microbiol 6:3257–3265. [PubMed][CrossRef]
25. Johnson RC, Ball CA, Pfeffer D, Simon MI. 1988. Isolation of the gene encoding the Hin recombinational enhancer binding protein. Proc Natl Acad Sci U S A 85:3484–3488. [PubMed][CrossRef]
26. Koch C, Kahmann R. 1986. Purification and properties of the Escherichia coli host factor required for inversion of the G segment in bacteriophage Mu. J Biol Chem 261:15673–15678. [PubMed]
27. Johnson RC, Simon MI. 1985. Hin-mediated site-specific recombination requires two 26 bp recombination sites and a 60 bp recombinational enhancer. Cell 41:781–791. [PubMed][CrossRef]
28. Haykinson MJ, Johnson RC. 1993. DNA looping and the helical repeat in vitro and in vivo: effect of HU protein and enhancer location on Hin invertasome assembly. EMBO J 12:2503–2512. [PubMed]
29. Bruist MF, Glasgow AC, Johnson RC, Simon MI. 1987. Fis binding to the recombinational enhancer of the Hin DNA inversion system. Genes Dev 1:762–772. [PubMed][CrossRef]
30. Johnson RC, Bruist MB, Glaccum MB, Simon MI. 1984. In vitro analysis of Hin-mediated site-specific recombination. Cold Spring Harb Symp Quant Biol 49:751–760. [PubMed][CrossRef]
31. Bruist MF, Simon MI. 1984. Phase variation and the Hin protein: in vivo activity measurements, protein overproduction, and purification. J Bacteriol 159:71–79. [PubMed]
32. Ball CA, Osuna R, Ferguson KC, Johnson RC. 1992. Dramatic changes in Fis levels upon nutrient upshift in Escherichia coli. J Bacteriol 174:8043–8056. [PubMed]
33. Lim HM, Simon MI. 1992. The role of negative supercoiling in Hin-mediated site-specific recombination. J Biol Chem 267:11176–11182. [PubMed]
34. Ó Cróinín T, Carroll RK, Kelly A, Dorman CJ. 2006. Roles for DNA supercoiling and the Fis protein in modulating expression of virulence genes during intracellular growth of Salmonella enterica serovar Typhimurium. Mol Microbiol 62:869–982. [PubMed][CrossRef]
35. Koch C, Mertens G, Rudt F, Kahmann R, Kanaar R, Plasterk RH, van de Putte P, Sandulache R, Kamp D. 1987. The invertible G segment, p 75–91. In Symonds N, Toussaint A, van de Putte P, Howe MM (ed), Phage Mu, 0 ed. Cold Spring Harbor Laboratory, New York, NY.
36. Hiestand-Nauer R, Iida S. 1983. Sequence of the site-specific recombinase gene Cin and of its substrates serving in the inversion of the C segment of bacteriophage P1. EMBO J 2:1733–1740. [PubMed]
37. Chow LT, Bukhari AI. 1976. The invertible DNA segments of coliphages Mu and P1 are identical. Virology 74:242–248. [PubMed][CrossRef]
38. Toussaint A, Lefebvre N, Scott JR, Cowan JA, de Bruijn F, Bukhari AI. 1978. Relationships between temperate phages Mu and P1. Virology 89:146–161. [PubMed][CrossRef]
39. Grundy FJ, Howe MM. 1984. Involvement of the invertible G segment in bacteriophage Mu tail fiber biosynthesis. Virology 134:296–317. [PubMed][CrossRef]
40. Howe MM, Schumm JW, Taylor AL. 1979. The S and U genes of bacteriophage Mu are located in the invertible G segment of Mu DNA. Virology 92:108–124. [PubMed][CrossRef]
41. Giphart-Gassler M, Plasterk RH, van de Putte P. 1982. G inversion in bacteriophage Mu: a novel way of gene splicing. Nature 297:339–342. [PubMed][CrossRef]
42. Kamp D, Kahmann R, Zipser D, Broker TR, Chow LT. 1978. Inversion of the G DNA segment of phage Mu controls phage infectivity. Nature 271:577–580. [PubMed][CrossRef]
43. van de Putte P, Cramer S, Giphart-Gassler M. 1980. Invertible DNA determines host specificity of bacteriophage Mu. Nature 286:218–222. [PubMed][CrossRef]
44. Plasterk RH, Brinkman A, van de Putte P. 1983. DNA inversions in the chromosome of Escherichia coli and in bacteriophage Mu: relationship to other site-specific recombination systems. Proc Natl Acad Sci U S A 80:5355–5358. [PubMed][CrossRef]
45. Iida S, Meyer J, Kennedy KE, Arber W. 1982. A site-specific, conservative recombination system carried by bacteriophage P1. Mapping the recombinase gene cin and the cross-over sites cix for the inversion of the C segment. EMBO J 1:1445–1453. [PubMed]
46. Iida S, Huber H, Hiestand-Nauer R, Meyer J, Bickle TA, Arber W. 1984. The bacteriophage P1 site-specific recombinase Cin: recombination events and DNA recognition sequences. Cold Spring Harb Symp Quant Biol 49:769–777. [PubMed][CrossRef]
47. Kahmann R, Rudt F, Koch C, Mertens G. 1985. G inversion in bacteriophage Mu DNA is stimulated by a site within the invertase gene and a host factor. Cell 41:771–780. [PubMed][CrossRef]
48. Huber HE, Iida S, Arber W, Bickle TA. 1985. Site-specific DNA inversion is enhanced by a DNA sequence element in cis. Proc Natl Acad Sci U S A 82:3776–3780. [PubMed][CrossRef]
49. Hubner P, Arber W. 1989. Mutational analysis of a prokaryotic recombinational enhancer element with two functions. EMBO J 8:577–585. [PubMed]
50. Haffter P, Bickle TA. 1987. Purification and DNA-binding properties of FIS and Cin, two proteins required for the bacteriophage P1 site-specific recombination system, cin. J Mol Biol 198:579–587. [PubMed][CrossRef]
51. Koch C, Vandekerckhove J, Kahmann R. 1988. Escherichia coli host factor for site-specific DNA inversion: cloning and characterization of the fis gene. Proc Natl Acad Sci U S A 85:4237–4241. [PubMed][CrossRef]
52. Kanaar R, van Hal JP, van de Putte P. 1989. The recombinational enhancer for DNA inversion functions independent of its orientation as a consequence of dyad symmetry in the Fis-DNA complex. Nucleic Acids Res 17:6043–6053. [PubMed][CrossRef]
53. Plasterk RH, Ilmer TA, Van de Putte P. 1983. Site-specific recombination by Gin of bacteriophage Mu: inversions and deletions. Virology 127:24–36. [PubMed][CrossRef]
54. Symonds N, Coelho A. 1978. Role of the G segment in the growth of phage Mu. Nature 271:573–574. [PubMed][CrossRef]
55. Kahmann R, Rudt F, Mertens G. 1984. Substrate and enzyme requirements for in vitro site-specific recombination in bacteriophage Mu. Cold Spring Harb Symp Quant Biol 49:285–294. [PubMed][CrossRef]
56. Plasterk RH, van de Putte P. 1984. Inversion of DNA in vivo and in vitro by Gin and Pin proteins. Cold Spring Harb Symp Quant Biol 49:295–300. [PubMed][CrossRef]
57. Komano T. 1999. Shufflons: multiple inversion systems and integrons. Annu Rev Genet 33:171–191. [PubMed][CrossRef]
58. Iida S, Sandmeier H, Hubner P, Hiestand-Nauer R, Schneitz K, Arber W. 1990. The Min DNA inversion enzyme of plasmid p15B of Escherichia coli 15T-: a new member of the Din family of site-specific recombinases. Mol Microbiol 4:991–997. [PubMed][CrossRef]
59. Sandmeier H, Iida S, Hubner P, Hiestand-Nauer R, Arber W. 1991. Gene organization in the multiple DNA inversion region min of plasmid p15B of E. coli 15T-: assemblage of a variable gene. Nucleic Acids Res 19:5831–5838. [PubMed][CrossRef]
60. Sandmeier H, Iida S, Meyer J, Hiestand-Nauer R, Arber W. 1990. Site-specific DNA recombination system Min of plasmid p15B: a cluster of overlapping invertible DNA segments. Proc Natl Acad Sci U S A 87:1109–1113. [PubMed][CrossRef]
61. Kamp D, Kahmann R. 1981. The relationship of two invertible segments in bacteriophage Mu and Salmonella typhimurium DNA. Mol Gen Genet 184:564–566. [PubMed][CrossRef]
62. Kutsukake K, Iino T. 1980. Inversions of specific DNA segments in flagellar phase variation of Salmonella and inversion systems of bacteriophages P1 and Mu. Proc Natl Acad Sci U S A 77:7338–7341. [PubMed][CrossRef]
63. Kutsukake K, Nakao T, Iino T. 1985. A gene for DNA invertase and an invertible DNA in Escherichia coli K-12. Gene 34:343–350. [PubMed][CrossRef]
64. van de Putte P, Plasterk R, Kuijpers A. 1984. A Mu Gin complementing function and an invertible DNA region in Escherichia coli K-12 are situated on the genetic element e14. J Bacteriol 158:517–522. [PubMed]
65. Klippel A, Cloppenborg K, Kahmann R. 1988. Isolation and characterization of unusual Gin mutants. EMBO J 7:3983–3989. [PubMed]
66. Scott TN, Simon MI. 1982. Genetic analysis of the mechanism of the Salmonella phase variation site specific recombination system. Mol Gen Genet 188:313–321. [PubMed][CrossRef]
67. Moskowitz IP, Heichman KA, Johnson RC. 1991. Alignment of recombination sites in Hin-mediated site-specific DNA recombination. Genes Dev 5:1635–1645. [PubMed][CrossRef]
68. Kennedy KE, Iida S, Meyer J, Stalhammar-Carlemalm M, Hiestand-Nauer R, Arber W. 1983. Genome fusion mediated by the site specific DNA inversion system of bacteriophage P1. Mol Gen Genet 189:413–421. [PubMed][CrossRef]
69. Cerdeno-Tarraga AM, Patrick S, Crossman LC, Blakely G, Abratt V, Lennard N, Poxton I, Duerden B, Harris B, Quail MA, Barron A, Clark L, Corton C, Doggett J, Holden MT, Larke N, Line A, Lord A, Norbertczak H, Ormond D, Price C, Rabbinowitsch E, Woodward J, Barrell B, Parkhill J. 2005. Extensive DNA inversions in the B. fragilis genome control variable gene expression. Science 307:1463–1465. [PubMed][CrossRef]
70. Kuwahara T, Yamashita A, Hirakawa H, Nakayama H, Toh H, Okada N, Kuhara S, Hattori M, Hayashi T, Ohnishi Y. 2004. Genomic analysis of Bacteroides fragilis reveals extensive DNA inversions regulating cell surface adaptation. Proc Natl Acad Sci U S A 101:14919–14924. [PubMed][CrossRef]
71. Patrick S, Parkhill J, McCoy LJ, Lennard N, Larkin MJ, Collins M, Sczaniecka M, Blakely G. 2003. Multiple inverted DNA repeats of Bacteroides fragilis that control polysaccharide antigenic variation are similar to the hin region inverted repeats of Salmonella typhimurium. Microbiology 149:915–924. [PubMed][CrossRef]
72. Krinos CM, Coyne MJ, Weinacht KG, Tzianabos AO, Kasper DL, Comstock LE. 2001. Extensive surface diversity of a commensal microorganism by multiple DNA inversions. Nature 414:555–558. [PubMed][CrossRef]
73. Coyne MJ, Weinacht KG, Krinos CM, Comstock LE. 2003. Mpi recombinase globally modulates the surface architecture of a human commensal bacterium. Proc Natl Acad Sci U S A 100:10446–10451. [PubMed][CrossRef]
74. Fletcher CM, Coyne MJ, Bentley DL, Villa OF, Comstock LE. 2007. Phase-variable expression of a family of glycoproteins imparts a dynamic surface to a symbiont in its human intestinal ecosystem. Proc Natl Acad Sci U S A 104:2413–2418. [PubMed][CrossRef]
75. Simon M, Zieg J, Silverman M, Mandel G, Doolittle R. 1980. Phase variation: evolution of a controlling element. Science 209:1370–1374. [PubMed][CrossRef]
76. Smith M, Thorpe H. 2002. Diversity in the serine recombinases. Mol Microbiol 44:299–307. [PubMed][CrossRef]
77. Liu CC, Huhne R, Tu J, Lorbach E, Droge P. 1998. The resolvase encoded by Xanthomonas campestris transposable element ISXc5 constitutes a new subfamily closely related to DNA invertases. Genes Cells 3:221–233. [PubMed][CrossRef]
78. McLean MM, Chang Y, Dhar G, Heiss JK, Johnson RC. 2013. Multiple interfaces between a serine recombinase and an enhancer control site-specific DNA inversion. Elife 2:e01211. [PubMed][CrossRef]
79. Canosa I, Lurz R, Rojo F, Alonso JC. 1998. beta Recombinase catalyzes inversion and resolution between two inversely oriented six sites on a supercoiled DNA substrate and only inversion on relaxed or linear substrates. J Biol Chem 273:13886–13891. [PubMed][CrossRef]
80. Janniere L, McGovern S, Pujol C, Petit MA, Ehrlich SD. 1996. In vivo analysis of the plasmid pAM beta 1 resolution system. Nucleic Acids Res 24:3431–3436. [PubMed][CrossRef]
81. Rojo F, Alonso JC. 1994. The beta recombinase from the Streptococcal plasmid pSM19035 represses its own transcription by holding the RNA polymerase at the promoter region. Nucleic Acids Res 22:1855–1860. [PubMed][CrossRef]
82. Rowland SJ, Dyke KG. 1989. Characterization of the staphylococcal beta-lactamase transposon Tn552. EMBO J 8:2761–2773. [PubMed]
83. Rowland SJ, Dyke KG. 1990. Tn552, a novel transposable element from Staphylococcus aureus. Mol Microbiol 4:961–975. [PubMed][CrossRef]
84. Alonso JC, Gutierrez C, Rojo F. 1995. The role of chromatin-associated protein Hbsu in beta-mediated DNA recombination is to facilitate the joining of distant recombination sites. Mol Microbiol 18:471–478. [PubMed][CrossRef]
85. Alonso JC, Weise F, Rojo F. 1995. The Bacillus subtilis histone-like protein Hbsu is required for DNA resolution and DNA inversion mediated by the beta recombinase of plasmid pSM19035. J Biol Chem 270:2938–2945. [PubMed][CrossRef]
86. Smith MC, Brown WR, McEwan AR, Rowley PA. 2010. Site-specific recombination by phiC31 integrase and other large serine recombinases. Biochem Soc Trans 38:388–394. [PubMed][CrossRef]
87. Smith MC. Phage-encoded Serine Integrases and Other Large Serine Recombinases. In Craig NL (ed.), Mobile DNA III. ASM Press, Washington, DC, in press.
88. Van Duyne GD, Rutherford K. 2013. Large serine recombinase domain structure and attachment site binding. Crit Rev Biochem Mol Biol 48:476–491. [PubMed][CrossRef]
89. Rutherford K, Yuan P, Perry K, Sharp R, Van Duyne GD. 2013. Attachment site recognition and regulation of directionality by the serine integrases. Nucleic Acids Res 41:8341–8356. [PubMed][CrossRef]
90. Rutherford K, Van Duyne GD. 2014. The ins and outs of serine integrase site-specific recombination. Curr Opin Struct Biol 24:125–131. [PubMed][CrossRef]
91. Kersulyte D, Mukhopadhyay AK, Shirai M, Nakazawa T, Berg DE. 2000. Functional organization and insertion specificity of IS607, a chimeric element of Helicobacter pylori. J Bacteriol 182:5300–5308. [PubMed][CrossRef]
92. Boocock MR, Rice PA. 2013. A proposed mechanism for IS607-family serine transposases. Mob DNA 4:24. [PubMed][CrossRef]
93. Kanaar R, van de Putte P, Cozzarelli NR. 1986. Purification of the Gin recombination protein of Escherichia coli phage Mu and its host factor. Biochim Biophys Acta 866:170–177. [PubMed][CrossRef]
94. Mertens G, Fuss H, Kahmann R. 1986. Purification and properties of the DNA invertase Gin encoded by bacteriophage Mu. J Biol Chem 261:15668–15672. [PubMed]
95. Kanaar R, Klippel A, Shekhtman E, Dungan JM, Kahmann R, Cozzarelli NR. 1990. Processive recombination by the phage Mu Gin system: implications for the mechanisms of DNA strand exchange, DNA site alignment, and enhancer action. Cell 62:353–366. [PubMed][CrossRef]
96. Plasterk RH, Kanaar R, van de Putte P. 1984. A genetic switch in vitro: DNA inversion by Gin protein of phage Mu. Proc Natl Acad Sci U S A 81:2689–2692. [PubMed][CrossRef]
97. Mertens G, Hoffmann A, Blocker H, Frank R, Kahmann R. 1984. Gin-mediated site-specific recombination in bacteriophage Mu DNA: overproduction of the protein and inversion in vitro. EMBO J 3:2415–2421. [PubMed]
98. Klippel A, Mertens G, Patschinsky T, Kahmann R. 1988. The DNA invertase Gin of phage Mu: formation of a covalent complex with DNA via a phosphoserine at amino acid position 9. EMBO J 7:1229–1237. [PubMed]
99. Chiu TK, Sohn C, Dickerson RE, Johnson RC. 2002. Testing water-mediated DNA recognition by the Hin recombinase. EMBO J 21:801–814. [PubMed][CrossRef]
100. Johnson RC, Bruist MF. 1989. Intermediates in Hin-mediated DNA inversion: a role for Fis and the recombinational enhancer in the strand exchange reaction. EMBO J 8:1581–1590. [PubMed]
101. Crisona NJ, Kanaar R, Gonzalez TN, Zechiedrich EL, Klippel A, Cozzarelli NR. 1994. Processive recombination by wild-type Gin and an enhancer-independent mutant. Insight into the mechanisms of recombination selectivity and strand exchange. J Mol Biol 243:437–457. [PubMed][CrossRef]
102. Reed RR, Moser CD. 1984. Resolvase-mediated recombination intermediates contain a serine residue covalently linked to DNA. Cold Spring Harb Symp Quant Biol 49:245–249. [PubMed][CrossRef]
103. Merickel SK, Haykinson MJ, Johnson RC. 1998. Communication between Hin recombinase and Fis regulatory subunits during coordinate activation of Hin-catalyzed site-specific DNA inversion. Genes Dev 12:2803–2816. [PubMed][CrossRef]
104. Heichman KA, Johnson RC. 1990. The Hin invertasome: protein-mediated joining of distant recombination sites at the enhancer. Science 249:511–517. [PubMed][CrossRef]
105. Kanaar R, Cozzarelli NR. 1992. Roles of supercoiled DNA structure in DNA transactions. Cur Opin Struct Biol 2:369–379. [CrossRef]
106. Haykinson MJ, Johnson LM, Soong J, Johnson RC. 1996. The Hin dimer interface is critical for Fis-mediated activation of the catalytic steps of site-specific DNA inversion. Curr Biol 6:163–177. [PubMed][CrossRef]
107. Sanders ER, Johnson RC. 2004. Stepwise dissection of the Hin-catalyzed recombination reaction from synapsis to resolution. J Mol Biol 340:753–766. [PubMed][CrossRef]
108. Glasgow AC, Bruist MF, Simon MI. 1989. DNA-binding properties of the Hin recombinase. J Biol Chem 264:10072–10082. [PubMed]
109. Heiss JK, Sanders ER, Johnson RC. 2011. Intrasubunit and intersubunit interactions controlling assembly of active synaptic complexes during Hin-catalyzed DNA recombination. J Mol Biol 411:744–764. [PubMed][CrossRef]
110. Mertens G, Klippel A, Fuss H, Blocker H, Frank R, Kahmann R. 1988. Site-specific recombination in bacteriophage Mu: characterization of binding sites for the DNA invertase Gin. EMBO J 7:1219–1227. [PubMed]
111. Yang W, Steitz TA. 1995. Crystal structure of the site-specific recombinase gammadelta resolvase complexed with a 34 bp cleavage site. Cell 82:193–207. [PubMed][CrossRef]
112. Mouw KW, Rowland SJ, Gajjar MM, Boocock MR, Stark WM, Rice PA. 2008. Architecture of a serine recombinase-DNA regulatory complex. Mol Cell 30:145–155. [PubMed][CrossRef]
113. Olorunniji FJ, Stark WM. 2009. The catalytic residues of Tn3 resolvase. Nucleic Acids Res 37:7590–7602. [PubMed][CrossRef]
114. Keenholtz RA, Rowland SJ, Boocock MR, Stark WM, Rice PA. 2011. Structural basis for catalytic activation of a serine recombinase. Structure 19:799–809. [PubMed][CrossRef]
115. Nanassy OZ, Hughes KT. 1998. In vivo identification of intermediate stages of the DNA inversion reaction catalyzed by the Salmonella Hin recombinase. Genetics 149:1649–1663. [PubMed]
116. Adams CW, Nanassy O, Johnson RC, Hughes KT. 1997. Role of arginine-43 and arginine-69 of the Hin recombinase catalytic domain in the binding of Hin to the hix DNA recombination sites. Mol Microbiol 24:1235–1247. [PubMed][CrossRef]
117. Dhar G, Heiss JK, Johnson RC. 2009. Mechanical constraints on Hin subunit rotation imposed by the Fis/enhancer system and DNA supercoiling during site-specific recombination. Mol Cell 34:746–759. [PubMed][CrossRef]
118. Dhar G, McLean MM, Heiss JK, Johnson RC. 2009. The Hin recombinase assembles a tetrameric protein swivel that exchanges DNA strands. Nucleic Acids Res 37:4743–4756. [PubMed][CrossRef]
119. Li W, Kamtekar S, Xiong Y, Sarkis GJ, Grindley ND, Steitz TA. 2005. Structure of a synaptic gamma delta resolvase tetramer covalently linked to two cleaved DNAs. Science 309:1210–1215. [PubMed][CrossRef]
120. Ritacco CJ, Kamtekar S, Wang J, Steitz TA. 2013. Crystal structure of an intermediate of rotating dimers within the synaptic tetramer of the G-segment invertase. Nucleic Acids Res 41:2673–2682. [PubMed][CrossRef]
121. Bruist MF, Horvath SJ, Hood LE, Steitz TA, Simon MI. 1987. Synthesis of a site-specific DNA-binding peptide. Science 235:777–780. [PubMed][CrossRef]
122. Feng JA, Johnson RC, Dickerson RE. 1994. Hin recombinase bound to DNA: the origin of specificity in major and minor groove interactions. Science 263:348–355. [PubMed][CrossRef]
123. Hughes KT, Gaines PC, Karlinsey JE, Vinayak R, Simon MI. 1992. Sequence-specific interaction of the Salmonella Hin recombinase in both major and minor grooves of DNA. EMBO J 11:2695–2705. [PubMed]
124. Sluka JP, Horvath SJ, Glasgow AC, Simon MI, Dervan PB. 1990. Importance of minor-groove contacts for recognition of DNA by the binding domain of Hin recombinase. Biochemistry 29:6551–6561. [PubMed][CrossRef]
125. Hughes KT, Youderian P, Simon MI. 1988. Phase variation in Salmonella: analysis of Hin recombinase and hix recombination site interaction in vivo. Genes Dev 2:937–948. [PubMed][CrossRef]
126. Ritacco CJ, Steitz TA, Wang J. 2014. Exploiting large non-isomorphous differences for phase determination of a G-segment invertase-DNA complex. Acta Crystallogr D Biol Crystallogr 70:685–693. [PubMed][CrossRef]
127. Kanaar R, van de Putte P, Cozzarelli NR. 1989. Gin-mediated recombination of catenated and knotted DNA substrates: implications for the mechanism of interaction between cis-acting sites. Cell 58:147–159. [PubMed][CrossRef]
128. Surette MG, Chaconas G. 1992. The Mu transpositional enhancer can function in trans: requirement of the enhancer for synapsis but not strand cleavage. Cell 68:1101–1108. [PubMed][CrossRef]
129. Pan CQ, Finkel SE, Cramton SE, Feng JA, Sigman DS, Johnson RC. 1996. Variable structures of Fis-DNA complexes determined by flanking DNA-protein contacts. J Mol Biol 264:675–695. [PubMed][CrossRef]
130. Stella S, Cascio D, Johnson RC. 2010. The shape of the DNA minor groove directs binding by the DNA-bending protein Fis. Genes Dev 24:814–826. [PubMed][CrossRef]
131. Johnson RC, Glasgow AC, Simon MI. 1987. Spatial relationship of the Fis binding sites for Hin recombinational enhancer activity. Nature 329:462–465. [PubMed][CrossRef]
132. Shao Y, Feldman-Cohen LS, Osuna R. 2008. Functional characterization of the Escherichia coli Fis-DNA binding sequence. J Mol Biol 376:771–785. [PubMed][CrossRef]
133. Kahramanoglou C, Seshasayee AS, Prieto AI, Ibberson D, Schmidt S, Zimmermann J, Benes V, Fraser GM, Luscombe NM. 2011. Direct and indirect effects of H-NS and Fis on global gene expression control in Escherichia coli. Nucleic Acids Res 39:2073–2091. [PubMed][CrossRef]
134. Cho BK, Knight EM, Barrett CL, Palsson BO. 2008. Genome-wide analysis of Fis binding in Escherichia coli indicates a causative role for A-/AT-tracts. Genome Res 18:900–910. [PubMed][CrossRef]
135. Yuan HS, Finkel SE, Feng JA, Kaczor-Grzeskowiak M, Johnson RC, Dickerson RE. 1991. The molecular structure of wild-type and a mutant Fis protein: relationship between mutational changes and recombinational enhancer function or DNA binding. Proc Natl Acad Sci U S A 88:9558–9562. [PubMed][CrossRef]
136. Kostrewa D, Granzin J, Koch C, Choe HW, Raghunathan S, Wolf W, Labahn J, Kahmann R, Saenger W. 1991. Three-dimensional structure of the E. coli DNA-binding protein FIS. Nature 349:178–180. [PubMed][CrossRef]
137. Safo MK, Yang WZ, Corselli L, Cramton SE, Yuan HS, Johnson RC. 1997. The transactivation region of the Fis protein that controls site-specific DNA inversion contains extended mobile beta-hairpin arms. EMBO J 16:6860–6873. [PubMed][CrossRef]
138. Cheng YS, Yang WZ, Johnson RC, Yuan HS. 2000. Structural analysis of the transcriptional activation region on Fis: crystal structures of six Fis mutants with different activation properties. J Mol Biol 302:1139–1151. [PubMed][CrossRef]
139. Osuna R, Finkel SE, Johnson RC. 1991. Identification of two functional regions in Fis: the N-terminus is required to promote Hin-mediated DNA inversion but not lambda excision. EMBO J 10:1593–1603. [PubMed]
140. Koch C, Ninnemann O, Fuss H, Kahmann R. 1991. The N-terminal part of the E. coli DNA binding protein FIS is essential for stimulating site-specific DNA inversion but is not required for specific DNA binding. Nucleic Acids Res 19:5915–5922. [PubMed][CrossRef]
141. Hancock SP, Ghane T, Cascio D, Rohs R, Di Felice R, Johnson RC. 2013. Control of DNA minor groove width and Fis protein binding by the purine 2-amino group. Nucleic Acids Res 41:6750–6760. [PubMed][CrossRef]
142. Perkins-Balding D, Dias DP, Glasgow AC. 1997. Location, degree, and direction of DNA bending associated with the Hin recombinational enhancer sequence and Fis-enhancer complex. J Bacteriol 179:4747–4753. [PubMed]
143. Johnson RC, Johnson LM, Schmidt JW, Gardner JF. 2005. Major nucleoid proteins in the structure and function of the Escherichia coli chromosome, p. 65–132. In Higgins NP (ed), The bacterial chromosome. ASM Press, Washington DC.
144. Browning DF, Grainger DC, Busby SJ. 2010. Effects of nucleoid-associated proteins on bacterial chromosome structure and gene expression. Curr Opin Microbiol 13:773–780. [PubMed][CrossRef]
145. Luijsterburg MS, Noom MC, Wuite GJ, Dame RT. 2006. The architectural role of nucleoid-associated proteins in the organization of bacterial chromatin: A molecular perspective. J Struct Biol 156:262–272. [PubMed][CrossRef]
146. Dillon SC, Dorman CJ. 2010. Bacterial nucleoid-associated proteins, nucleoid structure and gene expression. Nat Rev Microbiol 8:185–195. [PubMed][CrossRef]
147. Skoko D, Yan J, Johnson RC, Marko JF. 2005. Low-force DNA condensation and discontinuous high-force decondensation reveal a loop-stabilizing function of the protein Fis. Phys Rev Lett 95:208101. [PubMed][CrossRef]
148. Skoko D, Yoo D, Bai H, Schnurr B, Yan J, McLeod SM, Marko JF, Johnson RC. 2006. Mechanism of chromosome compaction and looping by the Escherichia coli nucleoid protein Fis. J Mol Biol 364:777–798. [PubMed][CrossRef]
149. Ishihama A, Kori A, Koshio E, Yamada K, Maeda H, Shimada T, Makinoshima H, Iwata A, Fujita N. 2014. Intracellular concentrations of 65 species of transcription factors with known regulatory functions in Escherichia coli. J Bacteriol 196:2718–2727. [PubMed][CrossRef]
150. Schneider R, Travers A, Kutateladze T, Muskhelishvili G. 1999. A DNA architectural protein couples cellular physiology and DNA topology in Escherichia coli. Mol Microbiol 34:953–964. [PubMed][CrossRef]
151. Weinstein-Fischer D, Elgrably-Weiss M, Altuvia S. 2000. Escherichia coli response to hydrogen peroxide: a role for DNA supercoiling, topoisomerase I and Fis. Mol Microbiol 35:1413–1420. [PubMed][CrossRef]
152. Richardson SM, Boles TC, Cozzarelli NR. 1988. The helical repeat of underwound DNA in solution. Nucleic Acids Res 16:6607–6616. [PubMed][CrossRef]
153. Bellomy GR, Record MTJ. 1990. Stable DNA loops in vivo and in vitro: Roles in gene regulation at a distance and in biophysical characterization of DNA. Prog Nucleic Acid Res Mol Biol 39:81–127. [CrossRef]
154. Hillyard DR, Edlund M, Hughes KT, Marsh M, Higgins NP. 1990. Subunit-specific phenotypes of Salmonella typhimurium HU mutants. J Bacteriol 172:5402–5407. [PubMed]
155. Wada M, Kutsukake K, Komano T, Imamoto F, Kano Y. 1989. Participation of the hup gene product in site-specific DNA inversion in Escherichia coli. Gene 76:345–352. [PubMed][CrossRef]
156. Paull TT, Haykinson MJ, Johnson RC. 1993. The nonspecific DNA-binding and -bending proteins HMG1 and HMG2 promote the assembly of complex nucleoprotein structures. Genes Dev 7:1521–1534. [PubMed][CrossRef]
157. Paull TT, Johnson RC. 1995. DNA looping by Saccharomyces cerevisiae high mobility group proteins NHP6A/B. Consequences for nucleoprotein complex assembly and chromatin condensation. J Biol Chem 270:8744–8754. [PubMed][CrossRef]
158. Dhar G, Sanders ER, Johnson RC. 2004. Architecture of the Hin synaptic complex during recombination: the recombinase subunits translocate with the DNA strands. Cell 119:33–45. [PubMed][CrossRef]
159. Leschziner AE, Grindley NDF. 2003. The architecture of the gamma delta resolvase crossover site synaptic complex revealed by using constrained DNA substrates. Mol Cell 12:775–781. [PubMed][CrossRef]
160. Sarkis GJ, Murley LL, Leschziner AE, Boocock MR, Stark WM, Grindley ND. 2001. A model for the gamma delta resolvase synaptic complex. Mol Cell 8:623–631. [PubMed][CrossRef]
161. Nollmann M, He J, Byron O, Stark WM. 2004. Solution structure of the Tn3 resolvase-crossover site synaptic complex. Mol Cell 16:127–137. [PubMed][CrossRef]
162. Kamtekar S, Ho RS, Cocco MJ, Li W, Wenwieser SV, Boocock MR, Grindley NDF, Steitz TA. 2006. Implications of structures of synaptic tetramers of gamma delta resolvase for the mechanism of recombination. Proc Natl Acad Sci U S A 103:10642–10647. [PubMed][CrossRef]
163. Yuan P, Gupta K, Van Duyne GD. 2008. Tetrameric structure of a serine integrase catalytic domain. Structure 16:1275–1286. [PubMed][CrossRef]
164. Kanaar R, van de Putte P, Cozzarelli NR. 1988. Gin-mediated DNA inversion: product structure and the mechanism of strand exchange. Proc Natl Acad Sci U S A 85:752–756. [PubMed][CrossRef]
165. Kahmann R, Mertens G, Klippel A, Brauer B, Rudt R, Koch C. 1987. The mechanism of G inversion, p 681–689. In McMacken R, Kelly TJ (ed), DNA replication and recombination, UCLA symposium on molecular and cellular biology, vol. 47, Alan R. Liss, Inc., New York, NY.
166. Merickel SK, Johnson RC. 2004. Topological analysis of Hin-catalysed DNA recombination in vivo and in vitro. Mol Microbiol 51:1143–1154. [PubMed][CrossRef]
167. Heichman KA, Moskowitz IP, Johnson RC. 1991. Configuration of DNA strands and mechanism of strand exchange in the Hin invertasome as revealed by analysis of recombinant knots. Genes Dev 5:1622–1634. [PubMed][CrossRef]
168. Deibler RW, Rahmati S, Zechiedrich EL. 2001. Topoisomerase IV, alone, unknots DNA in E. coli. Genes Dev 15:748–761. [PubMed][CrossRef]
169. Klippel A, Kanaar R, Kahmann R, Cozzarelli NR. 1993. Analysis of strand exchange and DNA binding of enhancer-independent Gin recombinase mutants. EMBO J 12:1047–1057. [PubMed]
170. Iida S, Hiestand-Nauer R. 1986. Localized conversion at the crossover sequences in the site-specific DNA inversion system of bacteriophage P1. Cell 45:71–79. [PubMed][CrossRef]
171. Iida S, Hiestand-Nauer R. 1987. Role of the central dinucleotide at the crossover sites for the selection of quasi sites in DNA inversion mediated by the site-specific Cin recombinase of phage P1. Mol Gen Genet 208:464–468. [PubMed][CrossRef]
172. Bai H, Sun M, Ghosh P, Hatfull GF, Grindley ND, Marko JF. 2011. Single-molecule analysis reveals the molecular bearing mechanism of DNA strand exchange by a serine recombinase. Proc Natl Acad Sci U S A 108:7419–7424. [PubMed][CrossRef]
173. Vologodskii A, Cozzarelli NR. 1996. Effect of supercoiling on the juxtaposition and relative orientation of DNA sites. Biophys J 70:2548–2556. [PubMed][CrossRef]
174. Vologodskii AV, Levene SD, Klenin KV, Frank-Kamenetskii M, Cozzarelli NR. 1992. Conformational and thermodynamic properties of supercoiled DNA. J Mol Biol 227:1224–1243. [PubMed][CrossRef]
175. Boles TC, White JH, Cozzarelli NR. 1990. Structure of plectonemically supercoiled DNA. J Mol Biol 213:931–951. [PubMed][CrossRef]
176. Marko JF. 1997. The internal ‘slithering’ dynamics of supercoiled DNA. Physica A 244:263–277. [CrossRef]
177. Oram M, Marko JF, Halford SE. 1997. Communications between distant sites on supercoiled DNA from non-exponential kinetics for DNA synapsis by resolvase. J Mol Biol 270:396–412. [PubMed][CrossRef]
178. Marko JF. 2001. Short note on the scaling behavior of communication by ‘slithering’ on a supercoiled DNA. Physica A 296:289–292. [CrossRef]
179. Vologodskii AV, Cozzarelli NR. 1994. Conformational and thermodynamic properties of supercoiled DNA. Annu Rev Biophys Biomol Struct 23:609–643. [PubMed][CrossRef]
180. Lee SY, Lee HJ, Lee H, Kim S, Cho EH, Lim HM. 1998. In vivo assay of protein-protein interactions in Hin-mediated DNA inversion. J Bacteriol 180:5954–5960. [PubMed]
181. Sessions RB, Oram M, Szczelkun MD, Halford SE. 1997. Random walk models for DNA synapsis by resolvase. J Mol Biol 270:413–425. [PubMed][CrossRef]
182. Stark WM, Grindley NDF, Hatfull GF, Boocock MR. 1991. Resolvase-catalysed reactions between res sites differing in the central dinucleotide of subsite I. EMBO J 10:3541–3548. [PubMed]
183. Ghosh P, Kim AI, Hatfull GF. 2003. The orientation of mycobacteriophage Bxb1 integration is solely dependent on the central dinucleotide of attP and attB. Mol Cell 12:1101–1111. [PubMed][CrossRef]
184. Mandali S, Dhar G, Avliyakulov NK, Haykinson MJ, Johnson RC. 2013. The site-specific integration reaction of Listeria phage A118 integrase, a serine recombinase. Mobile DNA 4:2. [PubMed][CrossRef]
185. Haffter P, Bickle TA. 1988. Enhancer-independent mutants of the Cin recombinase have a relaxed topological specificity. EMBO J 7:3991–3996. [PubMed]
186. Burke ME, Arnold PH, He J, Wenwieser SV, Rowland SJ, Boocock MR, Stark WM. 2004. Activating mutations of Tn3 resolvase marking interfaces important in recombination catalysis and its regulation. Mol Microbiol 51:937–948. [PubMed][CrossRef]
187. Rowland SJ, Boocock MR, McPherson AL, Mouw KW, Rice PA, Stark WM. 2009. Regulatory mutations in Sin recombinase support a structure-based model of the synaptosome. Mol Microbiol 74:282–298. [PubMed][CrossRef]
188. Arnold PH, Blake DG, Grindley NDF, Boocock MR, Stark WM. 1999. Mutants of Tn3 resolvase which do not require accessory binding sites for recombination activity. EMBO J 18:1407–1414. [PubMed][CrossRef]
189. Olorunniji FJ, He J, Wenwieser SV, Boocock MR, Stark WM. 2008. Synapsis and catalysis by activated Tn3 resolvase mutants. Nucleic Acids Res 36:7181–7191. [PubMed][CrossRef]
190. McGaughey GB, Gagne M, Rappe AK. 1998. pi-Stacking interactions. Alive and well in proteins. J Biol Chem 273:15458–15463. [PubMed][CrossRef]
191. Brocchieri L, Karlin S. 1994. Geometry of interplanar residue contacts in protein structures. Proc Natl Acad Sci U S A 91:9297–9301. [PubMed][CrossRef]
192. Lee HJ, Lee SY, Lee HM, Lim HM. 2001. Effects of dimer interface mutations in Hin recombinase on DNA binding and recombination. Mol Genet Genomics 266:598–607. [PubMed][CrossRef]
193. Cozzarelli NR, Krasnow MA, Gerrard SP, White JH. 1984. A topological treatment of recombination and topoisomerases. Cold Spring Harb Symp Quant Biol 49:383–400. [PubMed][CrossRef]
microbiolspec.MDNA3-0047-2014.citations
cm/3/1
content/journal/microbiolspec/10.1128/microbiolspec.MDNA3-0047-2014
Loading

Citations loading...

Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.MDNA3-0047-2014
2015-02-19
2017-03-24

Abstract:

Reversible site-specific DNA inversion reactions are widely distributed in bacteria and their viruses. They control a range of biological reactions that most often involve alterations of molecules on the surface of cells or phage. These programmed DNA rearrangements usually occur at a low frequency, thereby preadapting a small subset of the population to a change in environmental conditions, or in the case of phages, an expanded host range. A dedicated recombinase, sometimes with the aid of additional regulatory or DNA architectural proteins, catalyzes the inversion of DNA. RecA or other components of the general recombination-repair machinery are not involved. This chapter discusses site-specific DNA inversion reactions mediated by the serine recombinase family of enzymes and focuses on the extensively studied serine DNA invertases that are stringently controlled by the Fis-bound enhancer regulatory system. The first section summarizes biological features and general properties of inversion reactions by the Fis/enhancer-dependent serine invertases and the recently described serine DNA invertases in . Mechanistic studies of reactions catalyzed by the Hin and Gin invertases are then explored in more depth, particularly with regards to recent advances in our understanding of the function of the Fis/enhancer regulatory system. These include the steps leading to the formation of the active recombination complex (invertasome) containing the recombinase tetramer and Fis/enhancer element and the process of DNA strand exchange by rotation of synapsed subunit pairs within the invertasome. The role of DNA topological forces that function in concert with the Fis/enhancer controlling element in specifying the overwhelming bias for DNA inversion over deletion and intermolecular recombination is also discussed.

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

Full text loading...

/deliver/fulltext/microbiolspec/3/1/MDNA3-0047-2014.html?itemId=/content/journal/microbiolspec/10.1128/microbiolspec.MDNA3-0047-2014&mimeType=html&fmt=ahah

Figures

Image of FIGURE 1

Click to view

FIGURE 1

Genetic organization of Fis/enhancer-dependent DNA inversion systems. (A) The Hin system controlling flagellin synthesis in Typhimurium. codes for one of the alternatively expressed flagellins, and is a repressor of the flagellin gene located elsewhere on the chromosome. (B, C) The Gin and Cin systems from phages Mu and P1, which control phage host range. and ′ gene segments are alternatively fused in-frame to the gene segment. The S and U genes encode tail fiber proteins. (D) The complex Min locus from the p15B plasmid. The different gene segments are alternatively fused to the gene segment. In each case, the recombination sites are colored red, and the positions of the DNA invertases (red-orange) with their associated recombinational enhancer segments (blue) are denoted. P designates a promoter with the Typhimurium and genes being transcribed by the sigma 28 form of RNA polymerase. doi:10.1128/microbiolspec.MDNA3-0047-2014.f1

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Click to view

FIGURE 2

Fis/enhancer-dependent serine DNA invertase recombination sites. DNA sequences of recombination sites from the systems depicted in Fig. 1 are listed along with the consensus sequence at the top. Sequences matching the consensus are highlighted in cyan. doi:10.1128/microbiolspec.MDNA3-0047-2014.f2

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Click to view

FIGURE 3

Amino acid sequence alignment of the Hin and Gin DNA invertases together with γδ resolvase. Highly conserved residues among all serine recombinases are highlighted in magenta. The active site serine residue is shaded black. Highly conserved residues among Fis/enhancer-dependent DNA invertases are in cyan; many of these are conserved among the small serine recombinases. Yellow highlighted residues within the α-helix B region are those that contact enhancer DNA and within α-helix 1 of the DNA binding domain (Hin residues 139 to 190) are those that interact with Fis. Residue numbering is according to Hin. Asterisks denote residues where single substitutions result in strong gain-of-function activities, often resulting in Fis/enhancer-independence ( 65 , 109 , 185 ). Secondary structure designations are from γδ resolvase (residues 1 to 138; PDB: 1GDT) and Hin (residues 139 to 190; PDB: 1IJW). An alignment that includes additional Fis/enhancer-dependent DNA invertases along with other small serine recombinases is given in reference 2 . doi:10.1128/microbiolspec.MDNA3-0047-2014.f3

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

Click to view

FIGURE 4

Serine recombinase subfamilies. The domain architectures of serine recombinase subfamily members denoting the ∼100 amino acid residue catalytic domain containing the active site serine (S), the oligomerization helix E, and the DNA binding domain (DBD). The DNA binding regions of large serine recombinases can be quite large (300 to 450 residues) and consist of two discrete domains. The DNA invertases and resolvases are often grouped together as small serine recombinases. doi:10.1128/microbiolspec.MDNA3-0047-2014.f4

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5

Click to view

FIGURE 5

The Hin invertasome. Electron micrograph of an invertasome together with a schematic drawing of the structure. The invertasome structure was stabilized by crosslinking and supercoils removed prior to spreading onto the grid and low angle platinum shadowing ( 104 ). Hin subunits are rendered as translucent spheres; Fis subunits are rendered as ovals. sites are depicted as arrows and the enhancer segment is blue. doi:10.1128/microbiolspec.MDNA3-0047-2014.f5

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 6

Click to view

FIGURE 6

DNA inversion reaction pathway by Fis/enhancer-dependent serine invertases. In step (c) Hin dimers bound to and are associated with the Fis-bound enhancer at the base of a branch on supercoiled DNA. Formation of the Hin tetramer (d) generates an enzyme active for double strand cleavage and subunit rotation (e). Ligation and resolution of the complex (f) results in inversion of the DNA segment between recombination sites. doi:10.1128/microbiolspec.MDNA3-0047-2014.f6

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 7

Click to view

FIGURE 7

The serine DNA invertase dimer. Model of the Hin dimer bound to derived from the catalytic domain and oligomerization helix E of γδ resolvase (PDB: 1GDT) linked to the DNA binding domain (DBD) of Hin (PDB: 1IJW) is shown. The Ser10 active site residue and core nucleotides where DNA exchange occurs are colored red. Hinge residue Ser99 (Cα) is rendered as a dark red sphere. The sequence of showing the Hin cleavage sites (arrows) and core nucleotides (red) is given below. doi:10.1128/microbiolspec.MDNA3-0047-2014.f7

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 8

Click to view

FIGURE 8

The Hin DNA binding domain bound to the conserved half-site located within the invertible segment. (A) Sequence of with the locations of severe DNA binding mutations ( 99 , 123 ). (B) Hin DBD-DNA complex (PDB: 1IJW). Side chains of residues Arg140, Ser174, and Arg178 along with the two ordered water molecules (cyan spheres) that make critical bridging contacts between Hin and DNA atoms are shown. Conserved residues Gln151, Arg154, and Leu155 on α-helix 1 that contact Fis are also shown. (C) Schematic representation of sequence-specific contacts, including water bridged hydrogen bonding. doi:10.1128/microbiolspec.MDNA3-0047-2014.f8

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 9

Click to view

FIGURE 9

Fis and the recombinational enhancer. (A) Fis binding motif derived from footprinting, mutagenesis, genome-wide ChIP, and X-ray crystallography (see reference 130 ). Bases below the numbering are strongly inhibitory for binding. (B) Structure of the Fis dimer bound to a high affinity DNA segment (Fis residues 10 to 98; PDB: 3IV5). The sequence of the 15 bp core between ±7 (colored brown) is given below. Arg85 contacts the conserved guanines at the borders of the core sequence; Asn84 contacts the DNA backbone and often the base at ±4 and is responsible for the inhibitory effect of a thymine at this position (panel A). A subset of other important residues making DNA backbone contacts are colored grey. The Arg71 side chains, which are poorly resolved in most structures of DNA complexes, are shown oriented towards DNA. Bending of the flanking DNA segments varies depending on the DNA sequence. The triad of residues (Val16, Asp20, and Val22) near the tips of the mobile β-hairpin arms that contact DNA invertases are denoted for the cyan colored subunit. (C) Model of the enhancer. The two Fis dimers are docked onto the enhancer DNA sequence. The Fis β-hairpin arms are highlighted in red. The A/T-rich DNA segments contacted by the helix B regions of the DNA invertase tetramer in the invertasome are colored magenta ( 78 ). doi:10.1128/microbiolspec.MDNA3-0047-2014.f9

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 10

Click to view

FIGURE 10

Assembly of the Hin invertasome and subunit rotation. (A) -Hin dimers associated at the Fis-bound enhancer. Fis dimers are gold with their β-hairpin arms colored magenta. Hin α-helix B and α-helix 1 are colored red. (B) Pre-activated Hin tetramer intermediate (based on 3BVP) and (C) post-cleavage tetramer (based on 1ZR4). Side chains of residues from helix B that contact enhancer DNA are denoted. (D, E) Partial rotations (50° and 90°, respectively) of the top synaptic subunit pair and (F) complete subunit rotation to mediate the exchange of DNA strands. A movie depicting the assembly of the invertasome and DNA exchange by subunit rotation is provided in Video 2 of reference ( 78 ), from which these images are taken. Details of the models are described in references 78 , 109 , and 117 . doi:10.1128/microbiolspec.MDNA3-0047-2014.f10

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 11

Click to view

FIGURE 11

DNA topological changes during the inversion reaction. The starting complex (invertasome) between the two recombination sites (arrows) and the enhancer at the base of a plectonemic branch traps two negative DNA nodes (DNA depicted as a ribbon without supercoiling). Double strand cleavages and DNA exchange by the equivalent of a 180° clockwise rotation create a negative node but also introduce two half turns of helical twist that cancel the negative node. The recombinant configuration of DNA strands changes the trapped nodes to a positive sign resulting in an overall linking number change of +4. Node signs are determined by directionally tracing the entire path of the DNA molecule ( 193 ). By convention, a node is defined as negative when the DNA strand in front is pointed upwards and the strand underneath crosses in a rightward direction. A positive node is when the strand underneath crosses in a leftward direction. (Figure is modified from reference 105 ). doi:10.1128/microbiolspec.MDNA3-0047-2014.f11

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 12

Click to view

FIGURE 12

DNA topological changes during processive recombination by serine DNA invertases. Initially, the recombination sites (green and blue) are assembled at the enhancer DNA (brown) in the invertasome structure. The initial assembly depicts short and long loops between the recombination sites and enhancer as found in the Hin and Gin systems. The first DNA exchange by the equivalent of 180° rotations of DNA strands covalently linked to recombinase subunits generates inversion; these molecules have lost four negative supercoils (not shown) but no knot nodes are introduced. Subsequent processive rounds of DNA exchange generate knots of increasing complexity with the orientation of the invertible segment alternating between parental and inverted; these have all lost two negative supercoils. Multiple windings of DNA (processive DNA exchanges) are torsionally restricted as long as the enhancer remains associated with the recombination sites, but release of the enhancer removes this constraint. The structures of the knots, which have been confirmed by electron microscopy, are depicted below. doi:10.1128/microbiolspec.MDNA3-0047-2014.f12

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 13

Click to view

FIGURE 13

Synapsis and DNA exchange of recombination sites. (A) Synapsis of wild-type recombination sites in a parallel configuration as in the standard invertasome complex. DNA cleavage followed by exchange and ligation inverts the intervening DNA segment. (B) Synapsis where one recombination site contains a mutation (red) within the core nucleotides. DNA cleavage and a single exchange result in unpaired core nucleotides that cannot ligate. A second exchange is required for ligation, which reorients the intervening DNA segment into the starting (parental) configuration and generates a 3-noded knot ( Fig. 12 ). (C) Synapsis of wild-type recombination sites that are oriented in a directly repeated configuration. Most of the time the sites align in an antiparallel configuration within an invertasome structure (see Fig. 16 ), and the core nucleotides cannot base pair after the first DNA exchange. Ligation can occur after a second exchange back into the parental orientation creating a 3-noded knot as in panel B. doi:10.1128/microbiolspec.MDNA3-0047-2014.f13

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 14

Click to view

FIGURE 14

Site-directed crosslinking demonstrating subunit rotation within active Hin tetramers. Model of the Hin tetramer based on resolvase tetramer structures. The view is of the rotation interface with residues converted to cysteine for site-directed crosslinking rendered as colored spheres (Cβ atom). Rotations refer to the top subunit pair (gold and purple) relative to a fixed bottom subunit pair. M101C residues (orange spheres) from the gold and blue -diagonally located subunits are within range for crosslinking with a bis-thio reactive reagent containing an 8 Å spacer but becomes optimally positioned for crosslinking after a ∼20° clockwise (cw) rotation. Initial crosslinks at residue 101 are between gold and blue subunits, but with time, purple and blue crosslinked subunit products that are the result of subunit exchange become equally represented. Crosslinking between S94C residues (magenta spheres) requires either a counterclockwise (ccw) rotation of at least 20° (optimal between 40 to 70°) to link -diagonally positioned gold and blue subunits or a clockwise rotation of about 270° to link purple and blue subunits from an original dimer. Fis/enhancer-activated reactions on supercoiled DNA primarily form 94-94 crosslinks between purple and blue subunits (cw rotation), whereas crosslinks between gold and blue subunits (ccw rotation) are overrepresented initially in Fis/enhancer-independent reactions but then both products become equally represented. Red spheres mark residues within the C-terminal third of helix E that support robust crosslinking even though they can be up to 70 Å from their nearest partner; rotations of 90±15° in the cw or ccw direction are required to generate crosslinks. Fis/enhancer-activated reactions on supercoiled DNA primarily form crosslinks between purple and green subunits (cw rotation) containing helix E cysteines, whereas Fis/enhancer-independent reactions without DNA supercoiling form crosslinks between gold and green subunits (ccw) or purple and green subunits (cw) with the same kinetics. Dashed lines highlight the positions of Q134C residues at the C-terminal ends of helix E. The kinetics of crosslinking between residues at positions 101, 94, and the C-terminal end of helix E provide strong support for bidirectional subunit rotation within Fis/enhancer-independent reactions and for primarily single round cw rotation in Fis/enhancer-dependent reactions on negatively supercoiled DNA. Crosslinks between helix D residues like K72C (green spheres) readily form upon full assembly of the tetramer and do not block subunit rotation or DNA ligation. Details are provided in references 117 , 118 , and 158 . doi:10.1128/microbiolspec.MDNA3-0047-2014.f14

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 15

Click to view

FIGURE 15

The subunit rotation interface. Surfaces of rotating subunit pairs from the (A) Hin model (residues 2 to 134 based on PDB: 2GM4), (B) Gin X-ray structure (residues 2 to 125, PDB: 3UJ3), and (C) γδ resolvase X-ray structure (residues 1 to 132, PDB: 2GM4) are shown after alignment. Hydrophobic residues are colored yellow, acidic residues are red, basic residues are blue, and polar residues are green. A 1.6 Å probe was used to render the surfaces. Dashed circles demarking the rotating interface have a diameter of ∼20 Å. (D) Surface area overlap calculated for different clockwise rotational conformers from the Hin model; γδ resolvase gives a very similar pattern ( 117 , 119 ). Rotations of around 0 to 10° correspond to conformers where the DNA ends are in-line for ligation and conformers around 100° have the E-helices between dimer pairs in a parallel/antiparallel configuration. The Hin models are based on γδ resolvase structures (shown here based on 2GM4); comparison of subunit structures with those from resolvase tetramers (2GM4 or 1ZR4) give RMSD values of <0.7 Å over the peptide backbone (residues 1 to 120). Subunits from the Gin tetramer structure (3UJ3) exhibit RMSD values of 1.3 to 1.5 Å over the peptide backbone atoms from residues 3 to 120 and 1.1 to 1.4 Å over just the catalytic domains from the Hin models or γδ resolvase tetramers (1ZR4 or 2GM4). Much of the difference between Gin and resolvase structures or Hin models is over poorly resolved loops connecting β1 to αA and β2 to αB. doi:10.1128/microbiolspec.MDNA3-0047-2014.f15

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 16

Click to view

FIGURE 16

Products formed on substrates containing directly repeated recombination sites. Most synaptic complexes assemble in an invertasome structure as diagrammed in the top pathway, but the recombination sites are in an antiparallel orientation. The unpaired core nucleotides after a single DNA exchange prevent ligation ( Fig. 13C ). Ligation after two exchanges results in a knot containing three negative nodes ( Fig. 12 ), as shown in the electron micrograph of a trefoil generated by Hin. In the bottom pathway, which occurs rarely, the recombination sites assemble in parallel orientation that requires an additional DNA loop. This structure is energetically unfavorable on a negatively supercoiled substrate. A single DNA exchange results in a singly linked catenated deletion product, as shown in the micrograph. The DNA molecules were coated with RecA protein to facilitate visualization of the DNA nodes. doi:10.1128/microbiolspec.MDNA3-0047-2014.f16

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 17

Click to view

FIGURE 17

Residues regulating conformational transitions. (A) Hin dimer model depicting some of the residues where mutations have been isolated that control the dimer-tetramer transition. (B) Hin tetramer model (based on PDB: 2GM4) highlighting helix E residues Phe105 and Met109, whose side chains are located within the rotation interface and His107, whose side chain is predicted to stabilize the synaptic interface. (C) Subunit from the Hin dimer model showing helix E residues Phe104, Phe105, Phe106 (behind helix E), and Met109. The surface of the catalytic domain is also shown highlighting the pocket organized by residues surrounding Phe88. Residues around the Phe88 pocket where mutations lead to Fis/enhancer-independence are colored red. (D) Subunit from the Hin tetramer model rendered similarly as in panel C. Note that the side chains of Phe105 and Met109 have rotated away from the catalytic domain and are now within the rotation interface (panel B). Phe104 rotates away from the partner dimer subunit and becomes associated with the synaptic and rotation interfaces. Certain mutations at His87 (colored maroon) lead to strong Fis/enhancer-independence, and different substitutions of the hinge residue Ser99 generate various phenotypes (see text). (E) Subunit from the Gin tetramer X-ray structure (PDB: 3UJ3) in the reverse orientation as shown in panel D. Numbering of residues in Gin is one less than Hin. doi:10.1128/microbiolspec.MDNA3-0047-2014.f17

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.MDNA3-0047-2014
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