Strong minor groove base conservation in sequence logos implies DNA distortion or base flipping during replication and transcription initiation.

The sequence logo for DNA binding sites of the bacteriophage P1 replication protein RepA shows unusually high sequence conservation ( approximately 2 bits) at a minor groove that faces RepA. However, B-form DNA can support only 1 bit of sequence conservation via contacts into the minor groove. The high conservation in RepA sites therefore implies a distorted DNA helix with direct or indirect contacts to the protein. Here I show that a high minor groove conservation signature also appears in sequence logos of sites for other replication origin binding proteins (Rts1, DnaA, P4 alpha, EBNA1, ORC) and promoter binding proteins (sigma(70), sigma(D) factors). This finding implies that DNA binding proteins generally use non-B-form DNA distortion such as base flipping to initiate replication and transcription.

[1]  M. Record,et al.  DNA footprints of the two kinetically significant intermediates in formation of an RNA polymerase-promoter open complex: evidence that interactions with start site and downstream DNA induce sequential conformational changes in polymerase and DNA. , 1998, Journal of molecular biology.

[2]  T. Lindahl,et al.  Covalently closed circular duplex DNA of Epstein-Barr virus in a human lymphoid cell line. , 1976, Journal of molecular biology.

[3]  R J Roberts,et al.  On base flipping , 1995, Cell.

[4]  C. Speck,et al.  From footprint to toeprint: a close-up of the DnaA box, the binding site for the bacterial initiator protein DnaA. , 1997, Nucleic acids research.

[5]  R. Roberts,et al.  Disruption of the target G-C base-pair by the HhaI methyltransferase. , 1995, Gene.

[6]  Bruce Stillman,et al.  ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex , 1992, Nature.

[7]  D. Chattoraj,et al.  P1 plasmid replication. Role of initiator titration in copy number control. , 1986, Journal of molecular biology.

[8]  Walter Gilbert,et al.  E. coli RNA polymerase interacts homologously with two different promoters , 1980, Cell.

[9]  C. Wada,et al.  Crystal structure of a prokaryotic replication initiator protein bound to DNA at 2.6 Å resolution , 1999, The EMBO journal.

[10]  Michael Carey,et al.  DNA recognition by GAL4: structure of a protein-DNA complex , 1992, Nature.

[11]  R. Johnson,et al.  Stopped-flow kinetic analysis of the interaction of Escherichia coli RNA polymerase with the bacteriophage T7 A1 promoter. , 1998, Journal of molecular biology.

[12]  D. Chattoraj,et al.  Conformation of the origin of P1 plasmid replication. Initiator protein induced wrapping and intrinsic unstacking. , 1993, Journal of molecular biology.

[13]  W. Lipscomb,et al.  The crystal structure of Haelll methyltransferase covalently complexed to DNA: An extrahelical cytosine and rearranged base pairing , 1995, Cell.

[14]  Sierd Bron,et al.  Bacillus subtilis and its closest relatives: from genes to cells , 2001 .

[15]  Arthur Kornberg,et al.  The dnaA protein complex with the E. coli chromosomal replication origin (oriC) and other DNA sites , 1984, Cell.

[16]  N. Seeman,et al.  Sequence-specific Recognition of Double Helical Nucleic Acids by Proteins (base Pairs/hydrogen Bonding/recognition Fidelity/ion Binding) , 2022 .

[17]  H. Xu,et al.  Human DNA replication initiation factors, ORC and MCM, associate with oriP of Epstein–Barr virus , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  T. D. Schneider,et al.  The P1 phage replication protein RepA contacts an otherwise inaccessible thymine N3 proton by DNA distortion or base flipping. , 2001, Nucleic acids research.

[19]  R. D. Little,et al.  Initiation of latent DNA replication in the Epstein-Barr virus genome can occur at sites other than the genetically defined origin , 1995, Molecular and cellular biology.

[20]  Woody Rw,et al.  Salt-dependent binding of Escherichia coli RNA polymerase to DNA and specific transcription by the core enzyme and holoenzyme. , 1987 .

[21]  N. Heintz,et al.  Premature Structural Changes at Replication Origins in a Yeast Minichromosome Maintenance (MCM) Mutant* , 2000, The Journal of Biological Chemistry.

[22]  W. McClure,et al.  Searching for and predicting the activity of sites for DNA binding proteins: compilation and analysis of the binding sites for Escherichia coli integration host factor (IHF). , 1990, Nucleic acids research.

[23]  K. Carr,et al.  Open‐complex formation by the host initiator, DnaA, at the origin of P1 plasmid replication. , 1993, The EMBO journal.

[24]  T. D. Schneider,et al.  Reading of DNA sequence logos: prediction of major groove binding by information theory. , 1996, Methods in enzymology.

[25]  R. W. Davis,et al.  Isolation and characterisation of a yeast chromosomal replicator , 1979, Nature.

[26]  M. Guéron,et al.  Characterization of base-pair opening in deoxynucleotide duplexes using catalyzed exchange of the imino proton. , 1988, Journal of Molecular Biology.

[27]  R. Roberts,et al.  Hhal methyltransferase flips its target base out of the DNA helix , 1994, Cell.

[28]  M. Guéron,et al.  A single mode of DNA base-pair opening drives imino proton exchange , 1987, Nature.

[29]  A. Aiyar,et al.  The plasmid replicon of EBV consists of multiple cis‐acting elements that facilitate DNA synthesis by the cell and a viral maintenance element , 1998, The EMBO journal.

[30]  Jeffrey W. Roberts,et al.  Base-Specific Recognition of the Nontemplate Strand of Promoter DNA by E. coli RNA Polymerase , 1996, Cell.

[31]  Stephen K. Burley,et al.  Co-crystal structure of TBP recognizing the minor groove of a TATA element , 1993, Nature.

[32]  W. McClure,et al.  Mechanism and control of transcription initiation in prokaryotes. , 1985, Annual review of biochemistry.

[33]  H. Heumann,et al.  Influence of Mg2+ and Temperature on Formation of the Transcription Bubble* , 1997, The Journal of Biological Chemistry.

[34]  D. Chattoraj,et al.  Negative control of plasmid DNA replication by iterons. Correlation with initiator binding affinity. , 1994, The Journal of biological chemistry.

[35]  Missing-base and ethylation interference footprinting of P1 plasmid replication initiator. , 1994, Nucleic acids research.

[36]  T. Kelly,et al.  Regulation of chromosome replication. , 2000, Annual review of biochemistry.

[37]  T. D. Schneider,et al.  Sequence logos: a new way to display consensus sequences. , 1990, Nucleic acids research.

[38]  Steven Hahn,et al.  Crystal structure of a yeast TBP/TATA-box complex , 1993, Nature.

[39]  T. D. Schneider,et al.  A design for computer nucleic-acid-sequence storage, retrieval, and manipulation. , 1982, Nucleic acids research.

[40]  S. TD.,et al.  Information Content of Individual Genetic Sequences , 1998 .

[41]  Aaron D. Wyner,et al.  Claude Elwood Shannon: Collected Papers , 1993 .

[42]  D. Chattoraj,et al.  Replication control of plasmid P1 and its host chromosome: the common ground. , 1997, Progress in nucleic acid research and molecular biology.

[43]  A. Abeles P1 plasmid replication. Purification and DNA-binding activity of the replication protein RepA. , 1986, The Journal of biological chemistry.

[44]  T. Tullius,et al.  High-resolution footprints of the DNA-binding domain of Epstein-Barr virus nuclear antigen 1 , 1989, Molecular and cellular biology.

[45]  T. D. Schneider,et al.  Interdependence of the position and orientation of SoxS binding sites in the transcriptional activation of the class I subset of Escherichia coli superoxide‐inducible promoters , 1999, Molecular microbiology.

[46]  T. D. Schneider,et al.  Information content of binding sites on nucleotide sequences. , 1986, Journal of molecular biology.

[47]  T. D. Schneider,et al.  Features of spliceosome evolution and function inferred from an analysis of the information at human splice sites. , 1992, Journal of molecular biology.

[48]  J. Yates,et al.  Constitutive binding of EBNA1 protein to the Epstein‐Barr virus replication origin, oriP, with distortion of DNA structure during latent infection. , 1993, The EMBO journal.

[49]  Peter B. Dervan,et al.  Recognition of the four Watson–Crick base pairs in the DNA minor groove by synthetic ligands , 1998, Nature.

[50]  J. Diffley,et al.  Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC. , 1995, The EMBO journal.

[51]  H. Margalit,et al.  Compilation of E. coli mRNA promoter sequences. , 1993, Nucleic acids research.

[52]  A M Gronenborn,et al.  Minor groove-binding architectural proteins: structure, function, and DNA recognition. , 1998, Annual review of biophysics and biomolecular structure.

[53]  M. Schumacher,et al.  Crystal structure of LacI member, PurR, bound to DNA: minor groove binding by alpha helices. , 1994, Science.

[54]  R. Kornberg,et al.  A GAL family of upstream activating sequences in yeast: roles in both induction and repression of transcription. , 1986, The EMBO journal.

[55]  G. Stormo,et al.  Escherichia coli promoter sequences: analysis and prediction. , 1996, Methods in enzymology.

[56]  R. Sauer,et al.  The N-terminal arms of λ repressor wrap around the operator DNA , 1982, Nature.

[57]  M. O’Donnell,et al.  DNA–protein interactions: Two steps to binding replication origins? , 1996, Current Biology.

[58]  M. Mulks,et al.  Identification of an Actinobacillus pleuropneumoniae Consensus Promoter Structure , 2003, Journal of bacteriology.

[59]  T. D. Schneider,et al.  Using sequence logos and information analysis of Lrp DNA binding sites to investigate discrepancies between natural selection and SELEX. , 1999, Nucleic acids research.

[60]  G. Verdine The flip side of DNA methylation , 1994, Cell.

[61]  D. Ghisotti,et al.  Characterization of the oriI andoriII Origins of Replication in Phage-Plasmid P4 , 1999, Journal of Virology.

[62]  D C Rees,et al.  A structural basis for recognition of A.T and T.A base pairs in the minor groove of B-DNA. , 1998, Science.

[63]  A. F. Neuwald,et al.  Assembly , Operation , and Disassembly of Protein Complexes : A Class of Chaperone-Like ATPases Associated with the + AAA , 1999 .

[64]  C. Newlon,et al.  The structure and function of yeast ARS elements. , 1993, Current opinion in genetics & development.

[65]  T. D. Schneider,et al.  Evolution of biological information. , 2000, Nucleic acids research.

[66]  Richard J. Roberts,et al.  Crystal structure of the Hhal DNA methyltransferase complexed with S-adenosyl-l-methionine , 1993, Cell.

[67]  C. Miller,et al.  cis-acting components in the replication origin from ribosomal DNA of Saccharomyces cerevisiae , 1993, Molecular and cellular biology.

[68]  J. Diffley,et al.  Protein-DNA interactions at a yeast replication origin , 1992, Nature.

[69]  J. Helmann,et al.  DNA-melting at the Bacillus subtilis flagellin promoter nucleates near -10 and expands unidirectionally. , 1997, Journal of molecular biology.

[70]  T. D. Schneider,et al.  Sequence walkers: a graphical method to display how binding proteins interact with DNA or RNA sequences. , 1997, Nucleic acids research.

[71]  A. Klug,et al.  Sequence-dependent helical periodicity of DNA , 1981, Nature.

[72]  A. Kornberg,et al.  Duplex opening by dnaA protein at novel sequences in initiation of replication at the origin of the E. coli chromosome , 1988, Cell.

[73]  R. Roberts,et al.  Crystal structure of the HhaI DNA methyltransferase complexed with S-adenosyl-L-methionine. , 1993, Cell.

[74]  Anindya Dutta,et al.  Replication from oriP of Epstein-Barr Virus Requires Human ORC and Is Inhibited by Geminin , 2001, Cell.

[75]  Y. Itoh,et al.  Complete nucleotide sequence of mini-Rts1 and its copy mutant , 1984, Journal of bacteriology.

[76]  R. Dickerson,et al.  DNA bending: the prevalence of kinkiness and the virtues of normality. , 1998, Nucleic acids research.

[77]  E. Lanka,et al.  Bacteriophage P4 DNA replication. , 1995, FEMS microbiology reviews.

[78]  K. Kirkegaard,et al.  Changes in the DNA structure of the lac UV5 promoter during formation of an open complex with Escherichia coli RNA polymerase. , 1985, Biochemistry.

[79]  J. F. Thompson,et al.  Empirical estimation of protein-induced DNA bending angles: applications to lambda site-specific recombination complexes. , 1988, Nucleic acids research.

[80]  C. Newlon Two jobs for the origin replication complex. , 1993, Science.

[81]  L. Pearl,et al.  The structural basis of specific base-excision repair by uracil–DNA glycosylase , 1996, Nature.

[82]  E. Kremmer,et al.  Human origin recognition complex binds to the region of the latent origin of DNA replication of Epstein–Barr virus , 2001, The EMBO journal.

[83]  T. D. Schneider,et al.  Redox-dependent shift of OxyR-DNA contacts along an extended DNA-binding site: A mechanism for differential promoter selection , 1994, Cell.

[84]  W. McClure,et al.  Kinetics of open complex formation between Escherichia coli RNA polymerase and the lac UV5 promoter. Evidence for a sequential mechanism involving three steps. , 1985, Biochemistry.

[85]  Y. Kamio,et al.  Nucleotide sequence and copy control function of the extension of the incI region (incI-b) of Rts1 , 1988 .

[86]  P. Dehaseth,et al.  Open complex formation by Escherichia coli RNA polymerase: the mechanism of polymerase‐induced strand separation of double helical DNA , 1995, Molecular microbiology.

[87]  S. Bell,et al.  Architecture of the yeast origin recognition complex bound to origins of DNA replication , 1997, Molecular and cellular biology.

[88]  L. Loeb,et al.  Prokaryotic DNA polymerase I: evolution, structure, and "base flipping" mechanism for nucleotide selection. , 2001, Journal of molecular biology.

[89]  E. Scherzinger,et al.  Phage P4 alpha protein is multifunctional with origin recognition, helicase and primase activities. , 1993, The EMBO journal.

[90]  B. Stillman,et al.  Functional conservation of multiple elements in yeast chromosomal replicators , 1994, Molecular and cellular biology.

[91]  T D Schneider,et al.  High information conservation implies that at least three proteins bind independently to F plasmid incD repeats , 1992, Journal of bacteriology.

[92]  L. Frappier,et al.  The DNA segregation mechanism of Epstein–Barr virus nuclear antigen 1 , 2000, EMBO reports.

[93]  T. D. Schneider,et al.  Information analysis of sequences that bind the replication initiator RepA. , 1993, Journal of molecular biology.

[94]  P. Dehaseth,et al.  Protein-nucleic acid interactions during open complex formation investigated by systematic alteration of the protein and DNA binding partners. , 1999, Biochemistry.

[95]  D. Chattoraj,et al.  P1 plasmid replication: replicon structure. , 1984, Journal of molecular biology.

[96]  G. Hayward,et al.  Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region , 1985, Cell.

[97]  R. Pfuetzner,et al.  Crystal Structure of the DNA-Binding Domain of the Epstein–Barr Virus Origin-Binding Protein, EBNA1, Bound to DNA , 1996, Cell.

[98]  L. J. Peck,et al.  Sequence dependence of the helical repeat of DNA in solution , 1981, Nature.

[99]  A. Travers,et al.  Recognition of distorted DNA structures by HMG domains. , 2000, Current opinion in structural biology.

[100]  M. Jacquet,et al.  The kinetics of sigma subunit directed promoter recognition by E. coli RNA polymerase. , 1999, Journal of molecular biology.

[101]  A. Kornberg,et al.  Opening of the replication origin of Escherichia coli by DnaA protein with protein HU or IHF. , 1992, The Journal of biological chemistry.

[102]  A. Abeles,et al.  Protein-DNA interactions in regulation of P1 plasmid replication , 1989, Journal of bacteriology.

[103]  K. Kawa,et al.  Epstein-Barr virus--associated diseases in humans. , 2000, International journal of hematology.

[104]  Phoebe A Rice,et al.  Crystal Structure of an IHF-DNA Complex: A Protein-Induced DNA U-Turn , 1996, Cell.

[105]  L. Frappier,et al.  EBNA1 distorts oriP, the Epstein-Barr virus latent replication origin , 1992, Journal of virology.

[106]  R. Umek,et al.  Yeast regulatory sequences preferentially adopt a non-B conformation in supercoiled DNA. , 1987, Nucleic acids research.

[107]  T. D. Schneider,et al.  Information analysis of Fis binding sites. , 1997, Nucleic acids research.

[108]  T D Schneider,et al.  Excess information at bacteriophage T7 genomic promoters detected by a random cloning technique. , 1989, Nucleic acids research.

[109]  B. Stillman Initiation of chromosome replication in eukaryotic cells. , 1992, Harvey lectures.

[110]  Aled M. Edwards,et al.  Two Domains of the Epstein-Barr Virus Origin DNA-binding Protein, EBNA1, Orchestrate Sequence-specific DNA Binding* , 2000, The Journal of Biological Chemistry.

[111]  Thomas D. Schneider,et al.  Fast Multiple Alignment of Ungapped DNA Sequences Using Information Theory and a Relaxation Method , 1996, Discret. Appl. Math..

[112]  D. Williams,et al.  Easily unwound DNA sequences and hairpin structures in the Epstein-Barr virus origin of plasmid replication , 1993, Journal of virology.

[113]  V. Ramakrishnan,et al.  Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics , 2000, Nature.

[114]  M. Schaechter,et al.  In vivo studies of DnaA binding to the origin of replication of Escherichia coli. , 1989, The EMBO journal.