Biophysical Reviews

, Volume 8, Issue 3, pp 197–207 | Cite as

Protein-induced DNA linking number change by sequence-specific DNA binding proteins and its biological effects



Sequence-specific DNA-binding proteins play essential roles in many fundamental biological events such as DNA replication, recombination, and transcription. One common feature of sequence-specific DNA-binding proteins is to introduce structural changes to their DNA recognition sites including DNA-bending and DNA linking number change (ΔLk). In this article, I review recent progress in studying protein-induced ΔLk by several sequence-specific DNA-binding proteins, such as E. coli cAMP receptor protein (CRP) and lactose repressor (LacI). It was demonstrated recently that protein-induced ΔLk is an intrinsic property for sequence-specific DNA-binding proteins and does not correlate to protein-induced other structural changes, such as DNA bending. For instance, although CRP bends its DNA recognition site by 90°, it was not able to introduce a ΔLk to it. However, LacI was able to simultaneously bend and introduce a ΔLk to its DNA binding sites. Intriguingly, LacI also constrained superhelicity within LacI–lac O1 complexes if (−) supercoiled DNA templates were provided. I also discuss how protein-induced ΔLk help sequence-specific DNA-binding proteins regulate their biological functions. For example, it was shown recently that LacI utilizes the constrained superhelicity (ΔLk) in LacI-lac O1 complexes and serves as a topological barrier to constrain free, unconstrained (−) supercoils within the 401-bp DNA loop. These constrained (−) supercoils enhance LacI’s binding affinity and therefore the repression of the lac promoter. Other biological functions include how DNA replication initiators λ O and DnaA use the induced ΔLk to open/melt bacterial DNA replication origins.


DNA linking number change (ΔLk) lac repressor (LacI) cAMP receptor protein (CRP) λ O DNA-bending DNA topological barrier 



This work was supported by grants from the National Institutes of Health 1R15GM109254-01A1 (to F.L.).

Compliance with ethical standards

Conflicts of interest

Fenfei Leng declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Adhya S (1989) Multipartite genetic control elements: communication by DNA loop. Annu Rev Genet 23:227–250PubMedCrossRefGoogle Scholar
  2. Aiken CR, Fisher EW, Gumport RI (1991) The specific binding, bending, and unwinding of DNA by RsrI endonuclease, an isoschizomer of EcoRI endonuclease. J Biol Chem 266:19063–19069PubMedGoogle Scholar
  3. Amouyal M, Buc H (1987) Topological unwinding of strong and weak promoters by RNA polymerase. A comparison between the lac wild-type and the UV5 sites of Escherichia coli. J Mol Biol 195:795–808PubMedCrossRefGoogle Scholar
  4. Anders C, Niewoehner O, Duerst A, Jinek M (2014) Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease. Nature 513:569–573PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bae B, Davis E, Brown D, Campbell EA, Wigneshweraraj S, Darst SA (2013) Phage T7 Gp2 inhibition of Escherichia coli RNA polymerase involves misappropriation of sigma70 domain 1.1. Proc Natl Acad Sci U S A 110:19772–19777PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bates AD, Maxwell A (2005) DNA topology. Oxford University Press, OxfordGoogle Scholar
  7. Becker NA, Kahn JD, Maher LJ III (2005) Bacterial repression loops require enhanced DNA flexibility. J Mol Biol 349:716–730PubMedCrossRefGoogle Scholar
  8. Becker NA, Kahn JD, Maher LJ III (2007) Effects of nucleoid proteins on DNA repression loop formation in Escherichia coli. Nucleic Acids Res 35:3988–4000PubMedPubMedCentralCrossRefGoogle Scholar
  9. Becker NA, Peters JP, Maher LJ III, Lionberger TA (2013) Mechanism of promoter repression by Lac repressor-DNA loops. Nucleic Acids Res 41:156–166PubMedCrossRefGoogle Scholar
  10. Becker NA, Greiner AM, Peters JP, Maher LJ III (2014) Bacterial promoter repression by DNA looping without protein-protein binding competition. Nucleic Acids Res 42:5495–5504PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bell CE, Lewis M (2000) A closer view of the conformation of the Lac repressor bound to operator. Nat Struct Biol 7:209–214PubMedCrossRefGoogle Scholar
  12. Bertrand-Burggraf E, Schnarr M, Lefevre JF, Daune M (1984) Effect of superhelicity on the transcription from the tet promoter of pBR322. Abortive initiation and unwinding experiments. Nucleic Acids Res 12:7741–7752PubMedPubMedCentralCrossRefGoogle Scholar
  13. Bond LM, Peters JP, Becker NA, Kahn JD, Maher LJ III (2010) Gene repression by minimal lac loops in vivo. Nucleic Acids Res 38:8072–8082PubMedPubMedCentralCrossRefGoogle Scholar
  14. Busby S, Ebright RH (1999) Transcription activation by catabolite activator protein (CAP). J Mol Biol 293:199–213PubMedCrossRefGoogle Scholar
  15. Carra JH, Schleif RF (1993) Variation of half-site organization and DNA looping by AraC protein. EMBO J 12:35–44PubMedPubMedCentralGoogle Scholar
  16. Champoux JJ (2001) DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem 70:369–413PubMedCrossRefGoogle Scholar
  17. Chan B, Minchin S, Busby S (1990) Unwinding of duplex DNA during transcription initiation at the Escherichia coli galactose operon overlapping promoters. FEBS Lett 267:46–50PubMedCrossRefGoogle Scholar
  18. Chen B, Xiao Y, Liu C, Li C, Leng F (2010a) DNA linking number change induced by sequence-specific DNA-binding proteins. Nucleic Acids Res 38:3643–3654PubMedPubMedCentralCrossRefGoogle Scholar
  19. Chen B, Young J, Leng F (2010b) DNA bending by the mammalian high-mobility group protein AT hook 2. Biochemistry 49:1590–1595PubMedPubMedCentralCrossRefGoogle Scholar
  20. Chen Y, Zhang X, Dantas Machado AC, Ding Y, Chen Z, Qin PZ, Rohs R, Chen L (2013) Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion. Nucleic Acids Res 41:8368–8376PubMedPubMedCentralCrossRefGoogle Scholar
  21. Chung S-H (1996) Transcriptional activation of bacteriophage Lambda DNA replication. PhD dissertation, Johns Hopkins UniversityGoogle Scholar
  22. Muller-Hill B (1996) The Lac operon: a short history of a genetic paradigm. Walter de Gruyter, BerlinCrossRefGoogle Scholar
  23. Cozzarelli NR, Wang JC (1990) DNA topology and its biological effects. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
  24. Cozzarelli NR, Boles TC, White JH (1990) A primer on the topology and geometry of DNA supercoiling. In: Cozzarelli NR, Wang JC (eds) DNA topology and its biological effects. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 139–184Google Scholar
  25. Crothers DM, Gartenberg MR, Shrader TE (1991) DNA bending in protein-DNA complexes. Methods Enzymol 208:118–146PubMedCrossRefGoogle Scholar
  26. Ding Y, Manzo C, Fulcrand G, Leng F, Dunlap D, Finzi L (2014) DNA supercoiling: a regulatory signal for the lambda repressor. Proc Natl Acad Sci U S A 111:15402–15407PubMedPubMedCentralCrossRefGoogle Scholar
  27. Dodson M, Echols H, Wickner S, Alfano C, Mensa-Wilmot K, Gomes B, LeBowitz J, Roberts JD, McMacken R (1986) Specialized nucleoprotein structures at the origin of replication of bacteriophage lambda: localized unwinding of duplex DNA by a six- protein reaction. Proc Natl Acad Sci U S A 83:7638–7642PubMedPubMedCentralCrossRefGoogle Scholar
  28. Dodson M, McMacken R, Echols H (1989) Specialized nucleoprotein structures at the origin of replication of bacteriophage lambda. Protein association and disassociation reactions responsible for localized initiation of replication. J Biol Chem 264:10719–10725PubMedGoogle Scholar
  29. Douc-Rasy S, Kolb A, Prunell A (1989) Protein-induced unwinding of DNA: measurement by gel electrophoresis of complexes with DNA minicircles. Application to restriction endonuclease EcoRI, catabolite gene activator protein and lac repressor. Nucleic Acids Res 17:5173–5189PubMedPubMedCentralCrossRefGoogle Scholar
  30. Duderstadt KE, Berger JM (2013) A structural framework for replication origin opening by AAA+ initiation factors. Curr Opin Struct Biol 23:144–153PubMedCrossRefGoogle Scholar
  31. Duderstadt KE, Chuang K, Berger JM (2011) DNA stretching by bacterial initiators promotes replication origin opening. Nature 478:209–213PubMedPubMedCentralCrossRefGoogle Scholar
  32. Dunn TM, Hahn S, Ogden S, Schleif RF (1984) An operator at −280 base pairs that is required for repression of araBAD operon promoter: addition of DNA helical turns between the operator and promoter cyclically hinders repression. Proc Natl Acad Sci U S A 81:5017–5020PubMedPubMedCentralCrossRefGoogle Scholar
  33. Eismann ER, Muller-Hill B (1990) lac repressor forms stable loops in vitro with supercoiled wild-type lac DNA containing all three natural lac operators. J Mol Biol 213:763–775PubMedCrossRefGoogle Scholar
  34. Erzberger JP, Berger JM (2006) Evolutionary relationships and structural mechanisms of AAA+ proteins. Annu Rev Biophys Biomol Struct 35:93–114PubMedCrossRefGoogle Scholar
  35. Erzberger JP, Pirruccello MM, Berger JM (2002) The structure of bacterial DnaA: implications for general mechanisms underlying DNA replication initiation. EMBO J 21:4763–4773PubMedPubMedCentralCrossRefGoogle Scholar
  36. Erzberger JP, Mott ML, Berger JM (2006) Structural basis for ATP-dependent DnaA assembly and replication-origin remodeling. Nat Struct Mol Biol 13:676–683PubMedCrossRefGoogle Scholar
  37. Fisher LM (1982) DNA unwinding in transcription and recombination. Nature 299:105–106PubMedCrossRefGoogle Scholar
  38. Frederick CA, Grable J, Melia M, Samudzi C, Jen-Jacobson L, Wang BC, Greene P, Boyer HW, Rosenberg JM (1984) Kinked DNA in crystalline complex with EcoRI endonuclease. Nature 309:327–331PubMedCrossRefGoogle Scholar
  39. Fulcrand G, Chapagain P, Dunlap D, Leng F (2016a) Direct observation of a 91 bp LacI-mediated, negatively supercoiled DNA loop by atomic force microscope. FEBS Lett 590:613–618PubMedCrossRefGoogle Scholar
  40. Fulcrand G, Dages S, Zhi X, Chapagain P, Gerstman BS, Dunlap D, Leng F (2016b) DNA supercoiling, a critical signal regulating the basal expression of the lac operon in Escherichia coli. Sci Rep 6:19243PubMedPubMedCentralCrossRefGoogle Scholar
  41. Furth ME, Dove WF, Meyer BJ (1982) Specificity determinants for bacteriophage lambda DNA replication. III. Activation of replication in lambda ric mutants by transcription outside of ori. J Mol Biol 154:65–83PubMedCrossRefGoogle Scholar
  42. Gamper HB, Hearst JE (1982) A topological model for transcription based on unwinding angle analysis of E. coli RNA polymerase binary, initiation and ternary complexes. Cell 29:81–90PubMedCrossRefGoogle Scholar
  43. Gang J (2004) Measurement of DNA helical change for the binding of cyclic AMP receptor protein to lac DNA. Biochem Biophys Res Commun 322:993–997PubMedCrossRefGoogle Scholar
  44. Gartenberg MR, Crothers DM (1988) DNA sequence determinants of CAP-induced bending and protein binding affinity. Nature 333:824–829PubMedCrossRefGoogle Scholar
  45. Gasiunas G, Barrangou R, Horvath P, Siksnys V (2012) Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Acad Sci U S A 109:E2579–E2586PubMedPubMedCentralCrossRefGoogle Scholar
  46. Gaston K, Bell A, Busby S, Fried M (1992) A comparison of the DNA bending activities of the DNA binding proteins CRP and TFIID. Nucleic Acids Res 20:3391–3396PubMedPubMedCentralCrossRefGoogle Scholar
  47. Geanacopoulos M, Vasmatzis G, Zhurkin VB, Adhya S (2001) Gal repressosome contains an antiparallel DNA loop. Nat Struct Biol 8:432–436PubMedCrossRefGoogle Scholar
  48. Harley CB, Reynolds RP (1987) Analysis of E. coli promoter sequences. Nucleic Acids Res 15:2343–2361PubMedPubMedCentralCrossRefGoogle Scholar
  49. Hase T, Nakai M, Masamune Y (1989) Transcription of a region downstream from lambda ori is required for replication of plasmids derived from coliphage lambda. Mol Gen Genet 216:120–125PubMedCrossRefGoogle Scholar
  50. Horvath P, Barrangou R (2010) CRISPR/Cas, the immune system of bacteria and archaea. Science 327:167–170PubMedCrossRefGoogle Scholar
  51. Hsieh LS, Rouviere-Yaniv J, Drlica K (1991) Bacterial DNA supercoiling and [ATP]/[ADP] ratio: changes associated with salt shock. J Bacteriol 173:3914–3917PubMedPubMedCentralGoogle Scholar
  52. Hwang DS, Kornberg A (1992) Opening of the replication origin of Escherichia coli by DnaA protein with protein HU or IHF. J Biol Chem 267:23083–23086PubMedGoogle Scholar
  53. Jensen PR, Loman L, Petra B, van der Weijden C, Westerhoff HV (1995) Energy buffering of DNA structure fails when Escherichia coli runs out of substrate. J Bacteriol 177:3420–3426PubMedPubMedCentralGoogle Scholar
  54. Jiang F, Taylor DW, Chen JS, Kornfeld JE, Zhou K, Thompson AJ, Nogales E, Doudna JA (2016) Structures of a CRISPR-Cas9 R-loop complex primed for DNA cleavage. Science 351:867–871PubMedCrossRefGoogle Scholar
  55. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821PubMedCrossRefGoogle Scholar
  56. Kahn JD, Crothers DM (1998) Measurement of the DNA bend angle induced by the catabolite activator protein using Monte Carlo simulation of cyclization kinetics. J Mol Biol 276:287–309PubMedCrossRefGoogle Scholar
  57. Kercher MA, Lu P, Lewis M (1997) Lac repressor-operator complex. Curr Opin Struct Biol 7:76–85PubMedCrossRefGoogle Scholar
  58. Kim R, Kim SH (1983) Direct measurement of DNA unwinding angle in specific interaction between lac operator and repressor. Cold Spring Harb Symp Quant Biol 47(Pt 1):451–454PubMedCrossRefGoogle Scholar
  59. Kim R, Modrich P, Kim SH (1984) ‘Interactive’ recognition in EcoRI restriction enzyme-DNA complex. Nucleic Acids Res 12:7285–7292PubMedPubMedCentralCrossRefGoogle Scholar
  60. Kim J, Zwieb C, Wu C, Adhya S (1989) Bending of DNA by gene-regulatory proteins: construction and use of a DNA bending vector. Gene 85:15–23PubMedCrossRefGoogle Scholar
  61. Kolb A, Buc H (1982) Is DNA unwound by the cyclic AMP receptor protein? Nucleic Acids Res 10:473–485PubMedPubMedCentralCrossRefGoogle Scholar
  62. Kolb A, Spassky A, Chapon C, Blazy B, Buc H (1983) On the different binding affinities of CRP at the lac, gal and malT promoter regions. Nucleic Acids Res 11:7833–7852PubMedPubMedCentralCrossRefGoogle Scholar
  63. Kornberg A, Baker TA (1992) DNA replication. Freeman, New YorkGoogle Scholar
  64. Kramer H, Niemoller M, Amouyal M, Revet B, von Wilcken-Bergmann B, Muller-Hill B (1987) lac repressor forms loops with linear DNA carrying two suitably spaced lac operators. EMBO J 6:1481–1491PubMedPubMedCentralGoogle Scholar
  65. Kramer H, Amouyal M, Nordheim A, Muller-Hill B (1988) DNA supercoiling changes the spacing requirement of two lac operators for DNA loop formation with lac repressor. EMBO J 7:547–556PubMedPubMedCentralGoogle Scholar
  66. Leng F (2013) DNA bending by proteins: utilizing plasmid pBendAT as a tool. Methods Mol Biol 1054:267–282PubMedCrossRefGoogle Scholar
  67. Leng F, McMacken R (2002) Potent stimulation of transcription-coupled DNA supercoiling by sequence-specific DNA-binding proteins. Proc Natl Acad Sci U S A 99:9139–9144PubMedPubMedCentralCrossRefGoogle Scholar
  68. Leng F, Amado L, McMacken R (2004) Coupling DNA supercoiling to transcription in defined protein systems. J Biol Chem 279:47564–47571PubMedCrossRefGoogle Scholar
  69. Leng F, Chen B, Dunlap DD (2011) Dividing a supercoiled DNA molecule into two independent topological domains. Proc Natl Acad Sci U S A 108:19973–19978PubMedPubMedCentralCrossRefGoogle Scholar
  70. Leonard AC, Grimwade JE (2009) Initiating chromosome replication in E. coli: it makes sense to recycle. Genes Dev 23:1145–1150PubMedPubMedCentralCrossRefGoogle Scholar
  71. Leonard AC, Grimwade JE (2015) The orisome: structure and function. Front Microbiol 6:545PubMedPubMedCentralCrossRefGoogle Scholar
  72. Lewis M (2011) A tale of two repressors. J Mol Biol 409:14–27PubMedPubMedCentralCrossRefGoogle Scholar
  73. Lewis M (2013) Allostery and the lac operon. J Mol Biol 425:2309–2316PubMedCrossRefGoogle Scholar
  74. Lewis DE, Adhya S (2002) In vitro repression of the gal promoters by GalR and HU depends on the proper helical phasing of the two operators. J Biol Chem 277:2498–2504PubMedCrossRefGoogle Scholar
  75. Lewis M, Chang G, Horton NC, Kercher MA, Pace HC, Schumacher MA, Brennan RG, Lu P (1996) Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. Science 271:1247–1254PubMedCrossRefGoogle Scholar
  76. Lewis DE, Geanacopoulos M, Adhya S (1999) Role of HU and DNA supercoiling in transcription repression: specialized nucleoprotein repression complex at gal promoters in Escherichia coli. Mol Microbiol 31:451–461PubMedCrossRefGoogle Scholar
  77. Lia G, Bensimon D, Croquette V, Allemand JF, Dunlap D, Lewis DE, Adhya S, Finzi L (2003) Supercoiling and denaturation in Gal repressor/heat unstable nucleoid protein (HU)-mediated DNA looping. Proc Natl Acad Sci U S A 100:11373–11377PubMedPubMedCentralCrossRefGoogle Scholar
  78. Liu M, Gupte G, Roy S, Bandwar RP, Patel SS, Garges S (2003) Kinetics of transcription initiation at lacP1. Multiple roles of cyclic AMP receptor protein. J Biol Chem 278:39755–39761PubMedCrossRefGoogle Scholar
  79. Lobell RB, Schleif RF (1990) DNA looping and unlooping by AraC protein. Science 250:528–532PubMedCrossRefGoogle Scholar
  80. Lutter LC, Halvorson HR, Calladine CR (1996) Topological measurement of protein-induced DNA bend angles. J Mol Biol 261:620–633PubMedCrossRefGoogle Scholar
  81. Lyubchenko YL, Shlyakhtenko LS, Aki T, Adhya S (1997) Atomic force microscopic demonstration of DNA looping by GalR and HU. Nucleic Acids Res 25:873–876PubMedPubMedCentralCrossRefGoogle Scholar
  82. Magnan D, Bates D (2015) Regulation of DNA replication initiation by chromosome structure. J Bacteriol 197:3370–3377PubMedPubMedCentralCrossRefGoogle Scholar
  83. Maher LJ III (1998) Mechanisms of DNA bending. Curr Opin Chem Biol 2:688–694PubMedCrossRefGoogle Scholar
  84. Majumdar A, Rudikoff S, Adhya S (1987) Purification and properties of Gal repressor:pL-galR fusion in pKC31 plasmid vector. J Biol Chem 262:2326–2331PubMedGoogle Scholar
  85. Matthews KS (1992) DNA looping. Microbiol Rev 56:123–136PubMedPubMedCentralGoogle Scholar
  86. Matthews KS (1996) The whole lactose repressor. Science 271:1245–1246PubMedCrossRefGoogle Scholar
  87. Matthews KS, Nichols JC (1998) Lactose repressor protein: functional properties and structure. Prog Nucleic Acid Res Mol Biol 58:127–164PubMedCrossRefGoogle Scholar
  88. McKay DB, Steitz TA (1981) Structure of catabolite gene activator protein at 2.9 A resolution suggests binding to left-handed B-DNA. Nature 290:744–749PubMedCrossRefGoogle Scholar
  89. Mensa-Wilmot K, Carroll K, McMacken R (1989) Transcriptional activation of bacteriophage lambda DNA replication in vitro: regulatory role of histone-like protein HU of Escherichia coli. EMBO J 8:2393–2402PubMedPubMedCentralGoogle Scholar
  90. Mossing MC, Record MT Jr (1986) Upstream operators enhance repression of the lac promoter. Science 233:889–892PubMedCrossRefGoogle Scholar
  91. Mott ML, Berger JM (2007) DNA replication initiation: mechanisms and regulation in bacteria. Nat Rev Microbiol 5:343–354PubMedCrossRefGoogle Scholar
  92. Muller J, Oehler S, Muller-Hill B (1996) Repression of lac promoter as a function of distance, phase and quality of an auxiliary lac operator. J Mol Biol 257:21–29PubMedCrossRefGoogle Scholar
  93. Muller-Hill B (1998) The function of auxiliary operators. Mol Microbiol 29:13–18PubMedCrossRefGoogle Scholar
  94. Murakami KS (2013) X-ray crystal structure of Escherichia coli RNA polymerase sigma70 holoenzyme. J Biol Chem 288:9126–9134PubMedPubMedCentralCrossRefGoogle Scholar
  95. Nishimasu H, Ran FA, Hsu PD, Konermann S, Shehata SI, Dohmae N, Ishitani R, Zhang F, Nureki O (2014) Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell 156:935–949PubMedPubMedCentralCrossRefGoogle Scholar
  96. Oehler S, Eismann ER, Kramer H, Muller-Hill B (1990) The three operators of the lac operon cooperate in repression. EMBO J 9:973–979PubMedPubMedCentralGoogle Scholar
  97. Oehler S, Amouyal M, Kolkhof P, von Wilcken-Bergmann B, Muller-Hill B (1994) Quality and position of the three lac operators of E. coli define efficiency of repression. EMBO J 13:3348–3355PubMedPubMedCentralGoogle Scholar
  98. Passner JM, Steitz TA (1997) The structure of a CAP-DNA complex having two cAMP molecules bound to each monomer. Proc Natl Acad Sci U S A 94:2843–2847PubMedPubMedCentralCrossRefGoogle Scholar
  99. Rajewska M, Wegrzyn K, Konieczny I (2012) AT-rich region and repeated sequences - the essential elements of replication origins of bacterial replicons. FEMS Microbiol Rev 36:408–434PubMedCrossRefGoogle Scholar
  100. Ruff EF, Record MT Jr, Artsimovitch I (2015) Initial events in bacterial transcription initiation. Biomolecules 5:1035–1062PubMedPubMedCentralCrossRefGoogle Scholar
  101. Saiz L, Rubi JM, Vilar JM (2005) Inferring the in vivo looping properties of DNA. Proc Natl Acad Sci U S A 102:17642–17645PubMedPubMedCentralCrossRefGoogle Scholar
  102. Sander JD, Joung JK (2014) CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol 32:347–355PubMedPubMedCentralCrossRefGoogle Scholar
  103. Saucier JM, Wang JC (1972) Angular alteration of the DNA helix by E. coli RNA polymerase. Nat New Biol 239:167–170PubMedCrossRefGoogle Scholar
  104. Saviola B, Seabold RR, Schleif RF (1998) DNA bending by AraC: a negative mutant. J Bacteriol 180:4227–4232PubMedPubMedCentralGoogle Scholar
  105. Scherer G (1978) Nucleotide sequence of the O gene and of the origin of replication in bacteriophage lambda DNA. Nucleic Acids Res 5:3141–3156PubMedPubMedCentralCrossRefGoogle Scholar
  106. Schickor P, Metzger W, Werel W, Lederer H, Heumann H (1990) Topography of intermediates in transcription initiation of E.coli. EMBO J 9:2215–2220PubMedPubMedCentralGoogle Scholar
  107. Schleif R (2000) Regulation of the L-arabinose operon of Escherichia coli. Trends Genet 16:559–565PubMedCrossRefGoogle Scholar
  108. Schnos M, Zahn K, Inman RB, Blattner FR (1988) Initiation protein induced helix destabilization at the lambda origin: a prepriming step in DNA replication. Cell 52:385–395PubMedCrossRefGoogle Scholar
  109. Schnos M, Zahn K, Blattner FR, Inman RB (1989) DNA looping induced by bacteriophage lambda O protein: implications for formation of higher order structures at the lambda origin of replication. Virology 168:370–377PubMedCrossRefGoogle Scholar
  110. Schultz SC, Shields GC, Steitz TA (1991) Crystal structure of a CAP-DNA complex: the DNA is bent by 90 degrees. Science 253:1001–1007PubMedCrossRefGoogle Scholar
  111. Shanblatt SH, Revzin A (1986) The binding of catabolite activator protein and RNA polymerase to the Escherichia coli galactose and lactose promoters probed by alkylation interference studies. J Biol Chem 261:10885–10890PubMedGoogle Scholar
  112. Shi Y, Berg JM (1996) DNA unwinding induced by zinc finger protein binding. Biochemistry 35:3845–3848PubMedCrossRefGoogle Scholar
  113. Shimada T, Fujita N, Yamamoto K, Ishihama A (2011) Novel roles of cAMP receptor protein (CRP) in regulation of transport and metabolism of carbon sources. PLoS ONE 6, e20081PubMedPubMedCentralCrossRefGoogle Scholar
  114. Siebenlist U (1979) RNA polymerase unwinds an 11-base pair segment of a phage T7 promoter. Nature 279:651–652PubMedCrossRefGoogle Scholar
  115. Struble EB, Gittis AG, Bianchet MA, McMacken R (2007) Crystallization and preliminary crystallographic characterization of the origin-binding domain of the bacteriophage lambda O replication initiator. Acta Crystallogr Sect F: Struct Biol Cryst Commun 63:542–545CrossRefGoogle Scholar
  116. Swigon D, Coleman BD, Olson WK (2006) Modeling the Lac repressor-operator assembly: the influence of DNA looping on Lac repressor conformation. Proc Natl Acad Sci U S A 103:9879–9884PubMedPubMedCentralCrossRefGoogle Scholar
  117. van Workum M, van Dooren SJ, Oldenburg N, Molenaar D, Jensen PR, Snoep JL, Westerhoff HV (1996) DNA supercoiling depends on the phosphorylation potential in Escherichia coli. Mol Microbiol 20:351–360PubMedCrossRefGoogle Scholar
  118. Wang JC (1996) DNA topoisomerases. Annu Rev Biochem 65:635–692PubMedCrossRefGoogle Scholar
  119. Wang JC, Barkley MD, Bourgeois S (1974) Measurements of unwinding of lac operator by repressor. Nature 251:247–249PubMedCrossRefGoogle Scholar
  120. Wang JC, Jacobsen JH, Saucier JM (1977) Physiochemical studies on interactions between DNA and RNA polymerase. Unwinding of the DNA helix by Escherichia coli RNA polymerase. Nucleic Acids Res 4:1225–1241PubMedPubMedCentralCrossRefGoogle Scholar
  121. Weickert MJ, Adhya S (1993) The galactose regulon of Escherichia coli. Mol Microbiol 10:245–251PubMedCrossRefGoogle Scholar
  122. Westerhoff HV, O’Dea MH, Maxwell A, Gellert M (1988) DNA supercoiling by DNA gyrase. A static head analysis. Cell Biophys 12:157–181PubMedCrossRefGoogle Scholar
  123. White JH, Bauer WR (1986) Calculation of the twist and the writhe for representative models of DNA. J Mol Biol 189:329–341PubMedCrossRefGoogle Scholar
  124. White JH, Cozzarelli NR, Bauer WR (1988) Helical repeat and linking number of surface-wrapped DNA. Science 241:323–327PubMedCrossRefGoogle Scholar
  125. White JH, Gallo RM, Bauer WR (1992) Closed circular DNA as a probe for protein-induced structural changes. Trends Biochem Sci 17:7–12PubMedCrossRefGoogle Scholar
  126. Wolanski M, Donczew R, Zawilak-Pawlik A, Zakrzewska-Czerwinska J (2014) oriC-encoded instructions for the initiation of bacterial chromosome replication. Front Microbiol 5:735PubMedGoogle Scholar
  127. Wu HM, Crothers DM (1984) The locus of sequence-directed and protein-induced DNA bending. Nature 308:509–513PubMedCrossRefGoogle Scholar
  128. Wu HY, Liu LF (1991) DNA looping alters local DNA conformation during transcription. J Mol Biol 219:615–622PubMedCrossRefGoogle Scholar
  129. Zahn K, Blattner FR (1985) Binding and bending of the lambda replication origin by the phage O protein. EMBO J 4:3605–3616PubMedPubMedCentralGoogle Scholar
  130. Zinkel SS, Crothers DM (1990) Comparative gel electrophoresis measurement of the DNA bend angle induced by the catabolite activator protein. Biopolymers 29:29–38PubMedCrossRefGoogle Scholar
  131. Zuo Y, Steitz TA (2015) Crystal structures of the E. coli transcription initiation complexes with a complete bubble. Mol Cell 58:534–540PubMedCrossRefGoogle Scholar
  132. Zwieb C, Kim J, Adhya S (1989) DNA bending by negative regulatory proteins: Gal and Lac repressors. Genes Dev 3:606–611PubMedCrossRefGoogle Scholar

Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Biomolecular Sciences Institute and Department of Chemistry & BiochemistryFlorida International UniversityMiamiUSA

Personalised recommendations