Abstract
We have employed a combination of temperature-dependent UV absorption spectroscopy, circular dichroism, and batch calorimetry to characterize the binding of actinomycin D to a series of oligomeric DNA duplexes. We find the duplex [d(CGTCGACG)]2 to be unique in its ability to bind actinomycin D strongly despite the absence of a classic GpC site. We present evidence that this non-GpC-containing duplex binds two actinomycin D molecules in an apparently cooperative manner to form a complex that exhibits aberrant spectroscopic and calorimetric behavior. We propose that these observations are consistent with actinomycin D exhibiting a high-affinity, sequence-dependent DNA-binding mode distinct from its classic binding to isolated GpC sites.
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- Allen F. S., Gray D. M. The resolution of nucleic acid-ligand binding sites by CD first-neighbor analysis. Biopolymers. 1984 Nov;23(11 Pt 2):2661–2668. doi: 10.1002/bip.360231134. [DOI] [PubMed] [Google Scholar]
- Allen F. S., Jones M. B., Hollstein U. First-neighbor specificities of actinomycin-DNA bindings by circular dichroism. Biophys J. 1977 Oct;20(1):69–78. doi: 10.1016/S0006-3495(77)85537-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berman H. M. Hydration of nucleic acid crystals. Ann N Y Acad Sci. 1986;482:166–178. doi: 10.1111/j.1749-6632.1986.tb20948.x. [DOI] [PubMed] [Google Scholar]
- Berman H. M., Sowri A., Ginell S., Beveridge D. A systematic study of patterns of hydration in nucleic acids:(I) guanine and cytosine. J Biomol Struct Dyn. 1988 Apr;5(5):1101–1110. doi: 10.1080/07391102.1988.10506451. [DOI] [PubMed] [Google Scholar]
- Breslauer K. J., Frank R., Blöcker H., Marky L. A. Predicting DNA duplex stability from the base sequence. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3746–3750. doi: 10.1073/pnas.83.11.3746. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Breslauer K. J., Remeta D. P., Chou W. Y., Ferrante R., Curry J., Zaunczkowski D., Snyder J. G., Marky L. A. Enthalpy-entropy compensations in drug-DNA binding studies. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8922–8926. doi: 10.1073/pnas.84.24.8922. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown S. C., Mullis K., Levenson C., Shafer R. H. Aqueous solution structure of an intercalated actinomycin D-dATGCAT complex by two-dimensional and one-dimensional proton NMR. Biochemistry. 1984 Jan 31;23(3):403–408. doi: 10.1021/bi00298a003. [DOI] [PubMed] [Google Scholar]
- CAVALIERI L. F., NEMCHIN R. G. THE MODE OF INTERACTION OF ACTINOMYCIN D WITH DEOXYRIBONUCLEIC ACID. Biochim Biophys Acta. 1964 Aug 12;87:641–652. doi: 10.1016/0926-6550(64)90282-8. [DOI] [PubMed] [Google Scholar]
- Chen F. M. Binding specificities of actinomycin D to self-complementary tetranucleotide sequences -XGCY-. Biochemistry. 1988 Aug 23;27(17):6393–6397. doi: 10.1021/bi00417a030. [DOI] [PubMed] [Google Scholar]
- Chen F. M. Kinetic and equilibrium binding studies of actinomycin D with some d(TGCA)-containing dodecamers. Biochemistry. 1988 Mar 22;27(6):1843–1848. doi: 10.1021/bi00406a008. [DOI] [PubMed] [Google Scholar]
- Chou W. Y., Marky L. A., Zaunczkowski D., Breslauer K. J. The thermodynamics of drug-DNA interactions: ethidium bromide and propidium iodide. J Biomol Struct Dyn. 1987 Oct;5(2):345–359. doi: 10.1080/07391102.1987.10506399. [DOI] [PubMed] [Google Scholar]
- Crothers D. M., Sabol S. L., Ratner D. I., Müller W. Studies concerning the behavior of actinomycin in solution. Biochemistry. 1968 May;7(5):1817–1823. doi: 10.1021/bi00845a028. [DOI] [PubMed] [Google Scholar]
- Crothers D. M. Statistical thermodynamics of nucleic acid melting transitions with coupled binding equilibria. Biopolymers. 1971 Nov;10(11):2147–2160. doi: 10.1002/bip.360101110. [DOI] [PubMed] [Google Scholar]
- Dervan P. B. Design of sequence-specific DNA-binding molecules. Science. 1986 Apr 25;232(4749):464–471. doi: 10.1126/science.2421408. [DOI] [PubMed] [Google Scholar]
- Dickerson R. E., Drew H. R. Structure of a B-DNA dodecamer. II. Influence of base sequence on helix structure. J Mol Biol. 1981 Jul 15;149(4):761–786. doi: 10.1016/0022-2836(81)90357-0. [DOI] [PubMed] [Google Scholar]
- Fox K. R., Waring M. J. DNA structural variations produced by actinomycin and distamycin as revealed by DNAase I footprinting. Nucleic Acids Res. 1984 Dec 21;12(24):9271–9285. doi: 10.1093/nar/12.24.9271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GELLERT M., SMITH C. E., NEVILLE D., FELSENFELD G. ACTINOMYCIN BINDING TO DNA: MECHANISM AND SPECIFICITY. J Mol Biol. 1965 Mar;11:445–457. doi: 10.1016/s0022-2836(65)80001-8. [DOI] [PubMed] [Google Scholar]
- GOLDBERG I. H., RABINOWITZ M. Actionmycin D inhibition of deoxyribonucleic acid-dependent synthesis of ribonucleic acid. Science. 1962 Apr 27;136(3513):315–316. doi: 10.1126/science.136.3513.315. [DOI] [PubMed] [Google Scholar]
- GOLDBERG I. H., RABINOWITZ M., REICH E. Basis of actinomycin action. I. DNA binding and inhibition of RNA-polymerase synthetic reactions by actinomycin. Proc Natl Acad Sci U S A. 1962 Dec 15;48:2094–2101. doi: 10.1073/pnas.48.12.2094. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ginell S., Lessinger L., Berman H. M. The crystal and molecular structure of the anticancer drug actinomycin D--some explanations for its unusual properties. Biopolymers. 1988 May;27(5):843–864. doi: 10.1002/bip.360270511. [DOI] [PubMed] [Google Scholar]
- HAMILTON L. D., FULLER W., REICH E. X-ray diffraction and molecular model building studies of the interaction of actinomycin with nucleic acids. Nature. 1963 May 11;198:538–540. doi: 10.1038/198538b0. [DOI] [PubMed] [Google Scholar]
- HASELKORN R. ACTINOMYCIN D AS A PROBE FOR NUCLEIC ACID SECONDARY STRUCTURE. Science. 1964 Feb 14;143(3607):682–684. doi: 10.1126/science.143.3607.682. [DOI] [PubMed] [Google Scholar]
- Homer R. B. The circular dichroism of actinomycin D and its complexes with DNA and dGMP5'. Arch Biochem Biophys. 1969 Jan;129(1):405–407. doi: 10.1016/0003-9861(69)90193-3. [DOI] [PubMed] [Google Scholar]
- Jones R. L., Scott E. V., Zon G., Marzilli L. G., Wilson W. D. An NMR investigation of the binding of the anticancer drug actinomycin D to oligodeoxyribonucleotides with isolated 5'd(GC)3' binding sites. Biochemistry. 1988 Aug 9;27(16):6021–6026. doi: 10.1021/bi00416a029. [DOI] [PubMed] [Google Scholar]
- Krugh T. R., Neely J. W. Actinomycin D-mononucleotide interactions as studied by proton magnetic resonance. Biochemistry. 1973 Apr 24;12(9):1775–1782. doi: 10.1021/bi00733a018. [DOI] [PubMed] [Google Scholar]
- Krugh T. R., Wittlin F. N., Cramer S. P. Ethidium bromide-dinucleotide complexes. Evidence for intercalation and sequence preferences in binding to double-stranded nucleic acids. Biopolymers. 1975 Jan;14(1):197–210. doi: 10.1002/bip.1975.360140114. [DOI] [PubMed] [Google Scholar]
- Krugh T. R., Young M. A. Daunorubicin and adriamycin facilitate actinomycin D binding to poly(dA-dT)-poly(dA-dT). Nature. 1977 Oct 13;269(5629):627–628. doi: 10.1038/269627a0. [DOI] [PubMed] [Google Scholar]
- Marky L. A., Breslauer K. J. Calculating thermodynamic data for transitions of any molecularity from equilibrium melting curves. Biopolymers. 1987 Sep;26(9):1601–1620. doi: 10.1002/bip.360260911. [DOI] [PubMed] [Google Scholar]
- Marky L. A., Curry J., Breslauer K. J. Netropsin binding to polyd(AT) X polyd(AT) and to polydA X polydT: a comparative thermodynamic study. Prog Clin Biol Res. 1985;172B:155–173. [PubMed] [Google Scholar]
- Marky L. A., Snyder J. G., Remeta D. P., Breslauer K. J. Thermodynamics of drug-DNA interactions. J Biomol Struct Dyn. 1983 Oct;1(2):487–507. doi: 10.1080/07391102.1983.10507457. [DOI] [PubMed] [Google Scholar]
- Mudd C., Berger R. L., Hopkins H. P., Friauf W. S., Gibson C. An optimized differential heat conduction solution microcalorimeter for thermal kinetic measurements. J Biochem Biophys Methods. 1982 Aug;6(3):179–203. doi: 10.1016/0165-022x(82)90042-2. [DOI] [PubMed] [Google Scholar]
- Müller W., Crothers D. M. Studies of the binding of actinomycin and related compounds to DNA. J Mol Biol. 1968 Jul 28;35(2):251–290. doi: 10.1016/s0022-2836(68)80024-5. [DOI] [PubMed] [Google Scholar]
- Patel D. J. Peptide antibiotic-oligonucleotide interactions. Nuclear magnetic resonance investigations of complex formation between actinomycin D and d-ApTpGpCpApT in aqueous solution. Biochemistry. 1974 May 21;13(11):2396–2402. doi: 10.1021/bi00708a025. [DOI] [PubMed] [Google Scholar]
- Quadrifoglio F., Crescenzi V. On the binding of actinomycin and of daunomycin to DNA: a calorimetric and spectroscopic investigation. Biophys Chem. 1974 Jun;2(1):64–69. doi: 10.1016/0301-4622(74)80025-6. [DOI] [PubMed] [Google Scholar]
- Reid D. G., Salisbury S. A., Williams D. H. Proton nuclear overhauser effect study of the structure of an actinomycin D complex with a self-complementary tetranucleoside triphosphate. Biochemistry. 1983 Mar 15;22(6):1377–1385. doi: 10.1021/bi00275a009. [DOI] [PubMed] [Google Scholar]
- Scamrov A. V., Beabealashvilli R. S. Binding of actinomycin D to DNA revealed by DNase I footprinting. FEBS Lett. 1983 Nov 28;164(1):97–101. doi: 10.1016/0014-5793(83)80027-1. [DOI] [PubMed] [Google Scholar]
- Scott E. V., Jones R. L., Banville D. L., Zon G., Marzilli L. G., Wilson W. D. 1H and 31P NMR investigations of actinomycin D binding selectivity with oligodeoxyribonucleotides containing multiple adjacent d(GC) sites. Biochemistry. 1988 Feb 9;27(3):915–923. doi: 10.1021/bi00403a012. [DOI] [PubMed] [Google Scholar]
- Scott E. V., Zon G., Marzilli L. G., Wilson W. D. 2D NMR investigation of the binding of the anticancer drug actinomycin D to duplexed dATGCGCAT: conformational features of the unique 2:1 adduct. Biochemistry. 1988 Oct 4;27(20):7940–7951. doi: 10.1021/bi00420a053. [DOI] [PubMed] [Google Scholar]
- Sobell H. M., Jain S. C. Stereochemistry of actinomycin binding to DNA. II. Detailed molecular model of actinomycin-DNA complex and its implications. J Mol Biol. 1972 Jul 14;68(1):21–34. doi: 10.1016/0022-2836(72)90259-8. [DOI] [PubMed] [Google Scholar]
- Takusagawa F., Berman H. M. Some new aspects of actinomycin D-nucleic acid binding. Cold Spring Harb Symp Quant Biol. 1983;47(Pt 1):315–321. doi: 10.1101/sqb.1983.047.01.036. [DOI] [PubMed] [Google Scholar]
- Walker G. T., Stone M. P., Krugh T. R. Interaction of drugs with Z-DNA: cooperative binding of actinomycin D or actinomine to the left-handed forms of poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG-m5dC) reverses the conformation of the helix. Biochemistry. 1985 Dec 3;24(25):7471–7479. doi: 10.1021/bi00346a066. [DOI] [PubMed] [Google Scholar]
- Wells R. D., Larson J. E. Studies on the binding of actinomycin D to DNA and DNA model polymers. J Mol Biol. 1970 Apr 28;49(2):319–342. doi: 10.1016/0022-2836(70)90248-2. [DOI] [PubMed] [Google Scholar]
- Winkle S. A., Krugh T. R. Equilibrium binding of carcinogens and antitumor antibiotics to DNA: site selectivity, cooperativity, allosterism. Nucleic Acids Res. 1981 Jul 10;9(13):3175–3186. doi: 10.1093/nar/9.13.3175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamaoka K., Ziffer H. The optical properties of actinomycin D. II. Optical activity of the deoxyribonucleic acid complex. Biochemistry. 1968 Mar;7(3):1001–1008. doi: 10.1021/bi00843a018. [DOI] [PubMed] [Google Scholar]