Methoxyamine attack on cytosine produces ambivalent base pairing properties of the modified base

• Autorzy: Gdaniec Z. , Sowers L.C. , Fazakerley G.V.
• Języki publikacji: EN

Abstrakty

EN

We report the solution structure of two heptanucleotides each containing a central N4-methoxycytosine, in one case with adenine on the opposite strand and in the other with guanine. For the N4 -methoxycytosine-adenine pair only the imino form of the N4 -methoxycytosine residue is observed and base pairing is in Watson-Crick geometry. However, rotation of the methoxy group about the N-OCH3 bond is not constrained to a particular orientation although it must be anti to the N3 of .V,-methoxycytosine. The slow exchange on a proton NMR time scale between the single strand and double strand forms is attributed to the strong preference of the syn conformation of the OCH3 group in the single strand which inhibits base pair formation. For N4 -methoxycytosine base paired with guanosine we observe the N4 -methoxycytosine base in the amino form in Watson-Crick geometry and a slow exchange of this species with an imino form base paired in wobble geometry. The amino form is predominant at low temperature whereas the imino form predominates above 40°C. Our results point to preferential replacement of dTTP by N4 -me­thoxycytosine in primer elongation.

Słowa kluczowe

EN

tautomerism; methoxyamine attack; N-methoxycytosine; mutagenesis; cytosine; DNA

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1996
• Tom: 43
• Numer: 1
• Opis fizyczny: p.95-105,fig.

Twórcy

autor

Gdaniec Z.

• Polish Academy of Sciences, Z.Noskowskiego 12-14, 61-704 Poznan, Poland

autor

Sowers L.C.

autor

Fazakerley G.V.

Bibliografia

• 1. Anand. N.N., Brown, D.M. & Salisbury, S.A. (1987) The stability of oligodeoxyribonucieotide duplexes containing degenerate bases. Sucleic Acids Res. 15,8167-8176.
• 2. Kong Thoo I.in, P. & Brown, D.M. (1989) Synthesis and duplex stability of oligo­nucleotides containing cytosine-thymine analogues. Nucleic Acids Res. 17,10373-10383.
• 3. Stone, M.J., Nedderman, A.N.R., Williams, D.H., Kong Thoo I.in, P. & Brown, D.M. (1991) Molecular basis for methoxyamine initiated mutagenesis. 1H nuclear magnetic resonance studies of base-modified oligodeoxvnu- cleotides. J. Mol. Biol. 222, 711-723.
• 4. Van Meervelt, L., Moore, M.H., Kong Thoo I.in, P., Brown, D.M. & Kennard.O. (1990) Molecular and crystal structure of d(CGCGmo4C.C): /V1-methoxveytostne-guanine base-pairs in 2-DNA. /. Mol. Biol. 216, 773-781.
• 5. Fazakerley, G.V., Gdaniec, Z. & Sowers, L.C. (1993) Base-pair induced shifts in the tautomeric equilibrium of a modified DNA base. /. Mol. Biol. 230.6-10.
• 6. Nedderman. A.N.R., Stone, M.J., Williams, D.H., Kong Thoo I.in. P. & Brown, D.M. (1993) Molecular basis for methoxyamine-initiated mutagenesis: 'h nuclear magnetic resonance studies of oligonucleotide duplexes containing base-modified cytosine residues. /. Mol. Biol. 230,1068-1076.
• 7. Bodenhausen.G., Kogler,H.& Ernst, R.R. (1984) Selection of coherence-transfer pathways in N'MR pulse experiments. /. Magn. Reson. 58, 370-388.
• 8. Plateau, P. & Gueron. M. (1982) Exchangeable proton NMR without base-line distortion, using new strong-pulse sequences. /. Am. Chem. Soc. 104.7310-7311.
• 9. Davis, D.G. & Bax, A. (1985) Assingment of complex 'H NMR spectra via two-dimensional homonuclear Hartmann-l lahn spectroscopy. /. Am. Cheni. Soc. 107, 2820-2821.
• 10. Ranee, M., Sorensen, O.W., Bodenhausen, G„ Wagner. G., Ernst, R.R. & Wuthrich. K. (1983) Improved spectral resolution in COSY lH NMR spectra of proteins piu double quantum filtering. Biochem. Biophys. Res. Commun. 117,479—485.
• 11. Shaka. A.J. & Freeman, R. (1983) Simplification of NMR spectra by filtration through muitiple- quantum coherence. /. Magn. Reson. 51. 169- -173.
• 12. Piantini, U.. Sorensen, O.W. & F.rnst, R.R. (1982) Multiple quantum filters for elucidating NMR coupling networks. J. Am. Chem. Soc. 104, 6800-6801.
• 13. Bothner-By, A.A.,Stephens, R.L, l.ee,J., Warren. C.D. & Jeanloz, R.W. (1984) Structure deter­mination of a tetrasaccharide: transient nuclear Overhauser effects in the rotating frame. /. Chem. Soc. 106,811-813.
• 14. Bax, A. & Davis, D.G. (1985) Practical aspects of two-dimensional transverse NOE spectro­scopy. /. Magn. Reson. 63, 207-213.
• 15. Cuniasse, Ph., Sowers, L.C., Erit]a, A., Kaplan, B., Goodman, M.F., Cognet, J.A.H., Le Bret, M., Guschlbauer, W. & Fazakerley, G.V. (1989) Abasic frameshift in DNA. Solution con­formation determined by proton NMR and molecular mechanic calculations. Biochemistry 28, 2018-2026.
• 16. Brown, D.M., Hewlins, M.J.E &Schell, P. (1968) The tautomeric state of N(4)-hvdroxy- and N(4)- amino-cytosine derivatives. J. Chem. Soc. (C) 1923-1929.
• 17. Shugar. D., Huber.C.P. & Birnbaum,G. 1.(1976) Mechanism of hydroxvlamine mutagenesis. Crystal structure and conformation of 1,5-di- methyl-/V4-hvdroxycytosine. Biochim. Biophi/s. Acta 447,274-284. '
• 18. Engel, J.D. & von I Iippel, P.H. (1974) Effects of methylation on the stability of nucleic acid conformations: studies at the monomer level. Biochemistry 13, 4143-4158.
• 19. Fazakerley, G.V., Kraszewski, A., Teoule, R. & Guschlbauer, W. (1987) NMR and CD studies on an oligonucleotide containing N^methylcy- tosine. Nucleic Acids Res. 15, 2191-2201.
• 20. Reeves, S.T. & Beattie, K.L. (1985) Base-pairing properties of Yl-methoxydeoxvcytidine 5'-tri- phosphate during DNA synthesis on natural templates, catalvzcd by DŃA polymerase I of Escherichia coli. Biochemistry 24, 2262-2268.