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Nucleic Acids Research Pages 1509-1514

Conformational properties of DNA strands containing guanine-adenine and thymine-adenine repeats
Introduction
Materials And Methods
Results
Discussion
Acknowledgement
References


Conformational properties of DNA strands containing guanine-adenine and thymine-adenine repeats

Conformational properties of DNA strands containing guanine-adenine and thymine-adenine repeats Michaela Vorlícková*, Iva Kejnovská, Jirí Kovanda and Jaroslav Kypr

Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, CZ-612 65 Brno, Czech Republic

Received October 17, 1997; Revised and Accepted January 27, 1998

ABSTRACT

CD spectroscopy and PAGE were used to cooperatively analyze melting conformers of DNA strands containing GA and TA dinucleotide repeats. The 20mer (GA)10 formed a homoduplex in neutral solutions containing physiological concentrations of salts and this homoduplex was not destabilized even in the terminal (GA)3 hexamers of (GA)3(TA)4(GA)3, although the central (TA)4 portion of this oligonucleotide preserved the conformation adopted by (TA)10. This observation demonstrates that homoduplexes of alternating GA and TA sequences can co-exist in a single DNA molecule. Another 20mer, (GATA)5, adopted as a whole either the AT duplex, like (TA)10, or the GA duplex, like (GA)10, and switched between them reversibly. The concentration of salt controlled the conformational switching. Hence, guanine and thymine share significant properties regarding complementarity to adenine, while the TA and GA sequences can stack in at least two mutually compatible ways within the DNA duplexes analyzed here. These properties extend our knowledge of non-canonical structures of DNA.

INTRODUCTION

DNA can adopt conformations that do not contain Watson-Crick base pairs. While perhaps any pair of the canonical nucleic acid bases can be accommodated in DNA, interest has recently been mostly focused on purine·purine pairs, and G·A pairs in particular (reviewed in 1). The purine bases are large and it is therefore surprising how many possibilities exist for pairs of purine bases to be accommodated in the DNA double helix framework. These many possibilities undoubtedly underlie the extensive conformational polymorphism that is especially exhibited by alternating (GA)n sequences (2-12).

For decades a number of laboratories have been engaged in studying another alternating sequence containing an A in every other position, i.e. an alternating sequence of T and A. Though these two bases are complementary in the Watson-Crick sense, the conformational polymorphism this sequence confers on DNA is also extensive (see for example 13-20).

Here we address the question of compatibility of the conformers adopted by DNA molecules containing alternating GA and TA sequences. For this purpose we have studied the properties of several DNA oligonucleotides, mostly 20mers, whose pilot nucleotide sequences were as follows: (GA)10, (TA)10, (GA)3(TA)4(GA)3 and (GATA)5. The present study demonstrates that the conformers adopted by (GA)10 and (TA)10 can co-exist in (GA)3(TA)4(GA)3 and that (GATA)5 is a bi-stable molecule switching as a whole between the conformers stabilized by the TA and GA motifs.

MATERIALS AND METHODS

The oligonucleotides were synthesized, purified and characterized as described previously (21). Some of the oligonucleotides were prepared by Integrated DNA Technologies Inc. and bought from East Port (Prague, Czech Republic). The lyophilized oligonucleotides were dissolved in 1 mM Na phosphate, 0.3 mM EDTA, pH 7. Sample concentrations were determined from their absorption measured at 25°C in the above buffer and from the molar extinction coefficients given in Table 1. Only then were the required volumes of concentrated Na phosphate or Britton-Robinson buffer added to the oligonucleotide samples to obtain the conditions given in the figure captions. The molar extinction coefficients (Table 1) were determined from the molar extinction coefficients of single-stranded samples calculated according to Gray et al. (22) multiplied by the ratio of the absorbance of the sample at the absorption maximum at 25°C and the absorbance at 260 nm at 90°C. The UV absorption spectra were measured using a UNICAM 5625 UV/VIS spectrometer.

CD spectra were measured using Jobin-Yvon Mark IV and Mark VI spectrometers in Hellma cells placed in a thermostated holder. Ellipticity was expressed per M/cm, the molarity being related to the nucleoside residues in the DNA samples. The pH dependencies were measured in 1 cm path length cells at room temperature, while the titrations and pH measurements were undertaken directly in the cells. All other CD measurements were taken in 0.1 cm path length cells at the temperatures given in the figure captions. The sample absorption was always between 0.5 and 0.8 around 260 nm. Salt concentrations were increased by adding appropriate volumes of concentrated salt solutions or known weights of solid salts; in both cases the salt concentrations were corrected for the sample volume increase.

Non-denaturing PAGE was performed in a thermostated apparatus of submarine type (SE 600; Hoefer Scientific, San Francisco, CA). The polyacrylamide gels (20%, 29:1 monomer/bis ratio) had dimensions 14 × 16 × 0.1 cm. Electrophoresis was for 20 h at 70 V (~5 V/cm) in TBE (0.1 M Tris-borate, 2 mM EDTA), 100 or 300 mM NaCl at 0°C. The gels were stained with silver or methylene blue. Densitometry was performed using a Personal Densitometer SI, 375 A (Molecular Dynamics, Sunnyvale, CA).

Table 1. Oligonucleotides studied in this work, wavelengths of their absorption maxima and the oligonucleotide molar extinction coefficients at the absorption maxima at 25°C
Oligonucleotide Wavelength of absorption
maximum (nm)		 Extinction coefficient
(per M/cm)
(GA)10 255 11 820
(GA)3(TA)4(GA)3 258 10 250
(GATA)5 258 11 260
(TA)10 261 9730
(GA)5 255 11 450

RESULTS

At neutral pH and moderate ionic strength DNA strands containing alternating (GA)n sequences, e.g. (GA)10, associate into a cooperatively melting duplex whose CD spectrum is dominated by a positive band at 265 nm. Furthermore, it contains two negative bands at 290 and 245 nm (3; Fig. 1A). We call this conformer the neutral GA duplex. At neutral pH this type of CD spectrum was displayed not only by (GA)10 but also by (GA)3(TA)4(GA)3 (Fig. 1B), i.e. a (GA)10 analog whose four central guanines were replaced by thymines to give a central (TA)4 core. At low ionic strength this composite 20mer provided a weak CD spectrum corresponding to the CD spectrum calculated for the denatured oligonucleotide according to Cantor et al. (23). Increasing ionic strength (MgCl2, KCl or NaCl) induced a transition of (GA)3(TA)4(GA)3 accompanied by a marked increase in both its CD bands and their shift to shorter wavelengths (Fig. 1B). The diagnostic CD band at 265 nm of the limiting spectrum was smaller than with (GA)10 by a factor corresponding to the fraction of GA steps in the molecule. At room temperature the midpoints of the transition were at 1 and 2.5 mM MgCl2 and 120 and 180 mM NaCl with (GA)10 and (GA)3(TA)4(GA)3 respectively. The midpoints were identical in KCl and NaCl. The transitions were faster than processes whose kinetics can be measured by CD spectroscopy. Upon dilution the transitions were reversible.


Figure 1. NaCl-induced changes in the CD spectra of (GA)10 (left) and (GA)3(TA)4(GA)3 and (GA)5 (right). Concentrations of NaCl: (GA)10, ····· 0 (denatured oligonucleotide), - - - 0.1, - - 0.3 and -- 0.75 M; (GA)3(TA)4(GA)3, ····· 0 (denatured oligonucleotide) and -- 1.3 M NaCl; (GA)5, - · - 0.5 M NaCl. All measurements were in 10 mM Na phosphate, 0.3 mM EDTA, pH 7, at room temperature. (Insert) NaCl-induced changes in the CD spectra of (GA)10 (filled circles), (GA)3(TA)4(GA)3 (filled triangles) and (GA)5 (open circles) monitored by ellipticity at 265 nm.

The limiting CD spectrum of (GA)3(TA)4(GA)3 was remarkably similar to a linear combination of the CD spectra of (GA)10 and (TA)10 measured under the same conditions and weighted according to the number of GA and TA doublets in (GA)3(TA)4(GA)3 (Fig. 2). The correspondence was especially perfect around 260 nm, where the GA duplex provides the huge positive band. It follows from this observation that the central (TA)4 block did not suppress GA duplex formation in the flanking (GA)3 hexamers, though the (TA)4 block preserved the conformation adopted by (TA)10. Hence, the two conformations are compatible. This is interesting because, for example, the decamer (GA)5 exhibited a very weak response to increasing ionic strength (Fig. 1, insert). The GA duplex of (GA)5 was only stable at low temperature. Hence, the central (TA)4 octamer mediated stabilization of the GA duplexes in the two flanking (GA)3 blocks in the duplex of (GA)3(TA)4(GA)3.


Figure 2. A comparison of the measured (bold line) and calculated (bold dotted line) CD spectra of (GA)3(TA)4(GA)3. The calculated CD spectrum was obtained as a linear combination of the measured CD spectra of (GA)10 (light dotted CD spectrum) and (TA)10 (light uninterrupted CD spectrum), taking the numbers of the GA and TA steps in (GA)3(TA)4(GA)3 as the weights. The CD spectra were measured in 10 mM Na phosphate, 0.3 mM EDTA, pH 7, 0.75 M NaCl at 0°C.

Thermal stability (in 10 mM Na phosphate, 0.3 mM EDTA, 0.75 M NaCl, pH 7) was lower with the composite oligonucleotide (GA)3(TA)4(GA)3 (Tm 33°C) as compared with the parents (GA)10 (Tm 38°C) and (TA)10 (Tm 53°C). Its melting curve was monophasic. These data demonstrate that though the GA duplex is compatible with, and essentially uninfluenced by, the (TA)4 central block in (GA)3(TA)4(GA)3, the two junctions between the GA duplex and the AT duplex do cause minor destabilization of the composite oligonucleotide duplex.

At acid pH values the GA motif folds into a cooperatively melting conformer which is single-stranded at low ionic strength (4,6,8,12). We call it the acid GA fold. Its pH stability optimum is ~3.9 and the CD spectrum (Fig. 3, left) is surprisingly similar to the CD spectrum of the neutral GA duplex. However, the positive band around 260 nm is rather stronger and the negative band at 242 nm weaker, enhancing the non-conservative appearance of the CD spectrum, which may reflect increased base tilt (24). However, (TA)10 did not display any similar acid-induced changes and the CD spectrum of (GA)3(TA)4(GA)3 was certainly not reproduced by an appropriate combination of the CD spectra of (TA)10 and (GA)10 under these acidic pH conditions (Fig. 3, right and insert). Thus the thymines replacing the central guanines in the oligonucleotide destabilized the acid GA fold.


Figure 3. Changes in the CD spectra of (GA)10 (left) and (GA)3(TA)4(GA)3 (right) induced by acid pH. All of the CD spectra were measured in Britton-Robinson buffer in 1 cm path length cells at room temperature. Values of pH with (GA)10: ···· 7.1, - · - · - 5.0, - - - 4.3 and -- 3.9. Values of pH with (GA)3(TA)4(GA)3: ·····7.1, -- 4.1. (Insert) The pH-induced changes in the CD spectra of (GA)10 (circles) monitored by ellipticity at 262 nm and of (GA)3(TA)4(GA)3 (triangles) monitored at 268 nm.

The GA and TA motifs were further combined in another DNA 20mer, (GATA)5. At low salt, the CD spectrum of (GATA)5 corresponded to that calculated (23) for the single-stranded oligonucleotide. Adding salts, however, induced a two-state transition of (GATA)5 into a conformer whose CD spectrum contained a negative band at 288 nm, a positive band at 263 nm and another negative band at 248 nm (Fig. 4, left). This spectrum was different from the CD spectra provided by the GA duplexes. On the other hand, it was similar to the CD spectrum of poly(AT) and (TA)10 at high salt concentrations (Fig. 4, insert). The similarity was especially strong in the presence of CsCl or CsF, which are known to exert large sequence-specific effects on alternating sequences of A and T in DNA (15,16,21). That is why we call this structure of (GATA)5 the AT duplex, because the AT pairs stabilized this conformation while (GA)n formed no similar conformation. However, if the salt concentration was further increased then the CD spectrum of (GATA)5 started switching to exactly the CD spectrum of the GA duplex (Fig. 4, right). Hence, the TA doublets were able to adopt the GA duplex conformation, though we did not manage to switch (TA)10 to this conformer. The transition of (GATA)5 was two-state (the CD spectra measured within the transition had isoelliptic points at 230 and 255.5 nm) from the AT duplex to the neutral GA duplex and was reversible upon salt dilution.


Figure 4. NaCl-induced changes in the CD spectra of (GATA)5, reflecting its transition to the AT duplex (left) and the GA duplex (right). The CD spectra were measured at 0°C in 10 mM Tris-HCl, pH 7.1, plus (left) ····· 0 (single-stranded oligonucleotide), - - - 0.03, - - 0.07, and -- 0.59 M NaCl or plus (right) -- 0.59, ····· 2.3, - - 3.5 and - · - 5.0 M NaCl. (Insert) CD spectra of poly(AT) in 5 M NaCl (- - - ) or 4.7 M CsCl ( -- ) and of (TA)20 (bold dashed) in 5 M CsCl and (TA)10 (bold) in 5 M CsF.

Figure 5 compares salt-induced changes in the CD spectra of (GATA)5, (GA)10 and (TA)10. Up to decimolar NaCl concentrations (GATA)5 behaved like (TA)10, but was remarkably more ionic strength sensitive. On the other hand, molar NaCl concentrations caused transition of (GATA)5 to a conformer whose ellipticity reached the same value at 265 nm (the diagnostic band of the GA homoduplex), like the homoduplex of (GA)10.


Figure 5. NaCl-induced changes in the CD spectra of (GATA)5 (bold symbols), (TA)10 (open triangles) and (GA)10 (open circles). The changes were monitored through ellipticities at 275 (triangles) and 265 (circles) nm. Conditions were as in Figure 4.

The AT duplex of (GATA)5 was induced by all salts we tested, including MgCl2 (Fig. 6). Especially effective (inducing the deepest characteristic negative band at 290 nm) was not only CsF, but also LiCl, which is similarly known to induce large effects in the CD spectrum of poly(AT) (25). The AT duplex was stabilized at even lower concentrations of LiCl than CsF. The AT duplex could also arise in NaClO4, but only at low temperatures, because the chaotropic ClO4- anions destabilized DNA (26,27). The transition of (GATA)5 to the AT duplex took place within seconds, at most, and was reversible upon salt dilution with all examined salts. It is interesting that (GATA)5 generated the AT duplex more easily than the parent (TA)10. The 40mer (TA)20 assumed a conformer exhibiting a negative long wavelength band at 5 M NaCl or CsCl, while (TA)10 adopted it but only in concentrated CsF. Hence, the guanine, which presumably paired with adenine, stabilized the AT duplex of (GATA)5 remarkably.


Figure 6. Changes in the CD spectra of (GATA)5 induced by various salts monitored at 288 nm (lower curves), where the appearance of the negative CD band reflects formation of the AT duplex, and at 265 nm (upper curves), where the large increase in the positive CD band reflects formation of the GA duplex: MgCl2, bold triangles; NaCl, bold circles; LiCl, open circles; CsF, open triangles. Room temperature.

High concentrations of all examined salts also induced, at least partially, the transition of (GATA)5 from the AT duplex to the GA duplex. NaCl was the most effective salt inducing the GA duplex. LiCl and CsF were less effective (Fig. 6). In all cases the salt concentrations necessary to induce the neutral GA duplex of (GATA)5 were higher than for the GA duplex of (GA)10. Hence, thymine destabilizes the GA duplex, but conditions still existed when (GATA)5 isomerized to the GA duplex. Thus thymines could mimic guanines in the GA duplex, though it was certainly not their favored role. Unlike (GA)3(TA)4(GA)3, where the GA duplex only appeared in the terminal (GA)3 blocks, the GA duplex was adopted by the whole molecule of (GATA)5.

The GA duplex of (GATA)5 and the AT duplex of (GATA)5 were both destabilized by decreasing oligonucleotide concentration. In 1 mm path length cells (1 mM DNA concentration) the duplexes arose more easily (i.e. at lower salt concentrations) than in 50 mm path length cells, where the concentration of DNA was ~50 times lower. This was consistent with the duplex nature of both the GA duplex and the AT duplex, though the AT duplex could also take on the form of a unimolecular foldback (see below).

Figure 7 shows CD spectra of (GATA)5 during thermal denaturation recorded under conditions in which the oligonucleotide adopted the AT duplex (Fig. 7A) or the GA duplex (Fig. 7B). The GA duplex of (GATA)5 denatured cooperatively in a two-state manner (isoelliptic points at 231, 255.5 and 289.5 nm). This denaturation was very similar to the denaturation of (GA)10, including the values of [Delta]H (122 and 136 kJ/mol) calculated from the denaturation curves of (GA)10 and (GATA)5 respectively (Fig. 7, insert). In contrast, thermal melting of the AT duplex of (GATA)5 consisted of two steps, with only the second step reflecting denaturation. Temperature-induced changes were also exhibited by poly(AT) and partially by (TA)10 prior to denaturation (Fig. 7, insert). Consequently, the AT duplex of (GATA)5 behaved like DNA molecules containing an alternating sequence of T and A.


Figure 7. Temperature-induced changes in the CD spectra of (GATA)5 in 10 mM Na phosphate, 0.3 mM EDTA, pH 7, plus (A) 0.7 M NaCl (AT-duplex) and (B) 5 M NaCl (GA duplex). (A) 1-4, 0, 9, 19 and 25°C; 5-8, 39, 43, 50 and 68°C. (B) From the uninterrupted to the dotted line, 0, 25, 38 and 50°C. Note that the abscissa scales differ in (A) and (B). (Insert) Comparison of the temperature-induced changes in the CD spectra of the AT duplex of (GATA)5 (bold triangles) in 0.7 M NaCl and (TA)10 (open triangles) in 5 M NaCl (both monitored at 275 nm) and of (GA)10 (open circles) in 0.7 M NaCl and the GA duplex of (GATA)5 (bold circles) in 5 M NaCl (both monitored at 265 nm).


Figure 8. PAGE of the indicated oligonucleotides. (Left) The oligonucleotides were run in TBE buffer, 100 mM NaCl, pH 7, at 0°C. The gel was stained with silver. (Right) The oligonucleotides were run in TBE buffer, 300 mM NaCl, pH 7, at 0°C. The gel was stained with methylene blue.

(GATA)5 was also studied in acid solution. In contrast to (GA)10, but like (GA)3(TA)4(GA)3, it showed only very small acid-induced CD changes (not shown). Under the same conditions (GA)10 underwent cooperative transition to the acid GA fold (Fig. 3). Hence, thymine was not an acceptable substituent for guanine in the acid GA fold.

Figure 8 shows representative non-denaturing polyacrylamide gels of the above oligonucleotides run at pH 7, 0°C, at two ionic strengths. In 0.1 M NaCl (Fig. 8, left) (TA)10 migrated as two bands corresponding to a bimolecular duplex and a unimolecular foldback (28). The two bands were faint because the gel was stained with silver, which is a very good stain for (GA)n. The sample of (GA)10 migrated as a 20 bp homoduplex or as faster migrating species, because homoduplex formation was not complete at this ionic strength. As observed earlier (9), migration of the (GA)10 homoduplex was slower than migration of the homoduplex of (TA)10. The sample of (GATA)5, which according to CD isomerized to the AT duplex under the conditions of electrophoresis, showed a band at the position of the bimolecular duplex of (TA)10. A portion of (GATA)5 was a foldback and the remainder migrated between the two bands, probably reflecting partially folded single strands containing local hairpins. The gel shown on the left of Figure 8 was run at low salt to demonstrate foldbacks not only of (TA)10 but especially of (GATA)5. No foldbacks were formed by (GA)10. Foldback formation demonstrates an the antiparallel orientation of the GATA strands in the AT duplex. At higher salt concentrations the foldback bands dissappeared, as expected (Fig. 8, right), and all of the 20mers migrated as bimolecular duplexes.

DISCUSSION

This article deals with the DNA duplex conformations adopted by alternating GA and TA sequences. These conformations ought to be different because the participating bases are complementary in one case but not in the other. However, the present experiments demonstrate that the two conformers can co-exist in a single molecule without significant destabilization. In addition, depending on the solvent conditions, T can play the role of G and G can play the role of T in a DNA molecule composed of five repeats of (GATA). This possibility of mutual substitution allows (GATA)5 to associate in a bi-stable duplex that reversibly switches between two conformers, which we call the AT duplex and the GA duplex. The ionic strength of the oligonucleotide solution controls switching.

The GA motif confers a remarkable conformational polymorphism on DNA, including a tetraplex (2), a single-stranded acid fold (4,6,8), a parallel-stranded duplex (3), an antiparallel-stranded duplex (5,7), a zinc-specific duplex (9) and a tetraplex composed of two hairpins (10,11). However, molecular structures have been convincingly established for none of them and the conformational space of this motif also awaits systematic description. This work is in progress in our laboratory.

The AT motif is better characterized. An alternating B structure was suggested (13) for the low salt form of poly(AT). High NaCl or CsCl concentrations induce formation of duplexes of poly(AT), which provide a negative long wavelength CD band (16), like the AT duplex of (GATA)5. Proton NMR studies detected no departure from Watson-Crick base pairing in the high salt conformer of poly(AT) (29). As in the duplex of (TA)n, the strands are antiparallel in the AT duplex of (GATA)5, because both can exist as foldbacks. GA steps overwind DNA (30). The efficacy of cesium and lithium cations in stabilization of the high salt conformer of poly(TA) and the AT duplex of (GATA)5 is interesting in the light of the recently discovered extremely electronegative pocket at AT steps in DNA (31,32). CsF and LiCl stabilize the AT duplex of (GATA)5 much better than they stabilize its GA duplex (Fig. 6). In contrast, NaCl best stabilizes the GA duplex, whereas it is the worst inducer of the AT duplex. Probably increased stability of one conformer is an obstacle to the oligonucleotide switch to the other conformer. The transition between the AT duplex and GA duplex is two-state. The barrier between them may originate from different base pairing and/or different polarities of their strands in the duplexes.

It follows from the conformational bimorphism of (GATA)5 that G and T share significant properties regarding pair formation with A. In addition, GA and TA pairs can stack similarly or in mutually compatible ways in the double helix of DNA. This extends our understanding of the conformational variability of DNA. GA pairing is an interesting phenomenon not only from the conformational but also from the biological point of view. We have observed that the genome of HIV, the causative agent of AIDS, is extremely adenine-rich (33) and that the excess adenines were introduced into the HIV genome at the expense of cytosine (34). Remarkably, the C/A bias is the opposite of that in another human retrovirus, HTLV (34). GA pairing might explain the C/A compensation which, though less obvious, also exists in the human genome and the genomes of other organisms (35).

As shown here and elsewhere, some nucleotide motifs allow for DNA switching between distinct conformations. This fact demonstrates that transcription and translation are not the only means for genomic DNAs to express their genetic information. It is of interest in the context of this communication that (GATA)n microsatellites occur in the sex-determining part of the human Y chromosome (36) and that GATA sequences are genomic binding sites of a family of transcription factors (37).

ACKNOWLEDGEMENT

This work was supported by grant no. 204/95/1270 to M.V. from the Grant Agency of the Czech Republic.

REFERENCES

1. Chou,S.-H., Zhu,L. and Reid,B.R. (1997) Nucleic Acids Res., 267, 1055-1067.

2. Lee,J.S. (1990) Nucleic Acids Res., 18, 6057-6060. MEDLINE Abstract

3. Rippe,K., Fritsch,V., Westhof,E. and Jovin,T.M. (1992) EMBO J., 11, 3777-3786. MEDLINE Abstract

4. Dolinnaya,N.G. and Fresco,J.R. (1992) Proc. Natl. Acad. Sci. USA, 89, 9242-9246. MEDLINE Abstract

5. Huertas,D., Bellsolell,L., Casasnovas,J.M., Coll,M. and Azorín,F. (1993) EMBO J., 12, 4029-4038. MEDLINE Abstract

6. Dolinnaya,N.G., Braswell,E.H., Fossella,J.A., Klump,H. and Fresco,J.R. (1993) Biochemistry, 32, 10263-10270. MEDLINE Abstract

7. Casasnovas,J.M., Huertas,D., Ortiz-Lombardía,M., Kypr,J. and Azorín,F. (1993) J. Mol. Biol., 233, 671-681. MEDLINE Abstract

8. Shiber,M.C., Lavelle,L., Fossella,J.A. and Fresco,J.R. (1995) Biochemistry, 34, 14293-14299. MEDLINE Abstract

9. Ortiz-Lombardía,M., Eritja,R., Azorín,F., Kypr,J., Tejralová,I. and Vorlícková,M. (1995) Biochemistry, 34, 14408-14415. MEDLINE Abstract

10. Shiber,M.C., Braswell,E.H., Klump,H. and Fresco,J.R. (1996) Nucleic Acids Res., 24, 5004-5012. MEDLINE Abstract

11. Mukerji,I., Shiber,M.C., Fresco,J.R. and Spiro,T.G. (1996) Nucleic Acids Res., 24, 5013-5020. MEDLINE Abstract

12. Dolinnaya,N.G., Ulku,A. and Fresco,J.R. (1997) Nucleic Acids Res., 25, 1100-1107. MEDLINE Abstract

13. Klug,A., Jack,A.,Viswamitra,M.A., Kennard,O., Shakked,Z. and Steitz,T.A. (1979) J. Mol. Biol., 131, 669-680. MEDLINE Abstract

14. Shindo,H., Simpson,R.T. and Cohen,J.S. (1979) J. Biol. Chem., 254, 8125-8128. MEDLINE Abstract

15. Vorlícková,M., Sklenár,V. and Kypr,J. (1983) J. Mol. Biol., 166, 85-92. MEDLINE Abstract

16. Vorlícková,M. and Kypr,J. (1985) J. Biomol. Struct. Dyn., 3, 67-83. MEDLINE Abstract

17. Mahendrasingam,A., Forsyth,V.T., Hussain,R., Greenall,, Pigram,W.J. and Fuller,W. (1986) Science, 233, 195-197. MEDLINE Abstract

18. McClellan,J.A. and Lilley,D.M.J. (1991) J. Mol. Biol., 219, 145-149. MEDLINE Abstract

19. Yuan,H., Quintana,J. and Dickerson,R.E. (1992) Biochemistry, 31, 8009-8021. MEDLINE Abstract

20. Guzikevich-Guerstein,G. and Shakked,Z. (1996) Nature Struct. Biol., 3, 32-37.

21. Kypr,J., Chládková,J., Arnold,L., Sági,J., Szemzö,A. and Vorlícková,M. (1996) J. Biomol. Struct. Dyn., 13, 999-1006. MEDLINE Abstract

22. Gray,D.M., Hung,S.-H. and Johnson,K.H. (1995) Methods Enzymol., 246, 19-34. MEDLINE Abstract

23. Cantor,C.R., Warshaw,M.M. and Shapiro,H. (1970) Biopolymers, 9, 1059-1077. MEDLINE Abstract

24. Yang,J.T. and Samejima,T. (1968) Biochem. Biophys. Res. Commun., 33, 739-745. MEDLINE Abstract

25. Studdert,D.S., Patroni,M. and Davis,R.C. (1972) Biopolymers, 11, 761-779. MEDLINE Abstract

26. Breslow,R. and Guo,T. (1990) Proc. Natl. Acad. Sci. USA, 87, 167-169. MEDLINE Abstract

27. Vorlícková,M. (1995) Biophys. J., 69, 2033-2043. MEDLINE Abstract

28. Kovanda,J., Kejnovsky,E., Arnold,L. and Kypr,J. (1996) J. Biomol. Struct. Dyn., 14, 57-65. MEDLINE Abstract

29. Patel,D.J., Kozlowski,S.A., Suggs,J.W. and Cox,S.D. (1981) Proc. Natl. Acad. Sci. USA, 78, 4063-4067. MEDLINE Abstract

30. Chou,S.-H., Zhu,L. and Reid,B.R. (1997) J. Mol. Biol., 267, 1055-1067. MEDLINE Abstract

31. Young,M.A., Jayram,B. and Beveridge,D.L. (1997) J. Am. Chem. Soc., 119, 59-69.

32. Cheatham,T.E. and Kollman,P.A. (1997) J. Am. Chem. Soc., 119, 4805-4825.

33. Kypr,J. and Mrázek,J. (1987) Nature, 327, 20-20. MEDLINE Abstract

34. Kypr,J., Mrázek,J. and Reich,J. (1989) Biochim. Biophys. Acta, 1009, 280-282. MEDLINE Abstract

35. Mrázek,J. and Kypr,J. (1995) Comp. Appl. Biosci., 11, 195-199. MEDLINE Abstract

36. Roewer,L., Arnemann,J., Spurr,N.K., Grzeschik,K.-H. and Epplen,J.T. (1992) Hum. Genet., 89, 389-394. MEDLINE Abstract

37. Joulin,V. and Richard-Foy,H. (1995) Eur. J. Biochem., 232, 620-626. MEDLINE Abstract

*To whom correspondence should be addressed. Tel: +4205 4151 7188; Fax: +4205 4124 0497; Email: mifi@ibp.cz

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