Nucleic Acids Research, 2000, Vol. 28, No. 13 2613-2626
© 2000 Oxford University Press
New insights into the structure of abasic DNA from molecular dynamics simulations
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, 7000 East Avenue, L-448, Livermore, CA 94550, USA and 1School of Pharmacy, University of Maryland, Baltimore, MD, USA
Abasic (AP) sites constitute a common form of DNA damage, arising from the spontaneous or enzymatic breakage of the N-glycosyl bond and the loss of a nucleotide base. To examine the effects of such damage on DNA structure, especially in the vicinity of the abasic sugar, four 1.5 ns molecular dynamics simulations of double-helical DNA dodecamers with and without a single abasic (tetrahydrofuran, X) lesion in a 5'-d(CXT) context have been performed and analyzed. The results indicate that the abasic site does not maintain a hole or gap in the DNA, but instead perturbs the canonical structure and induces additional flexibility close to the abasic site. In the apurinic simulations (i.e., when a pyrimidine is opposite the AP site), the abasic sugar flipped in and out of the minor groove, and the gap was water filled, except during the occurrence of a novel non-Watson–Crick C-T base pair across the abasic site. The apyrimidinic gap was not penetrated by water until the abasic sugar flipped out and remained extrahelical. Both AP helices showed kinks of 20–30° at the abasic site. The Watson–Crick hydrogen bonds are more transient throughout the DNA double helices containing an abasic site. The abasic sugar displayed an unusually broad range of sugar puckers centered around the northern pucker. The increased motion of the bases and backbone near the abasic site appear to correlate with sequence-dependent helical stability. The data indicate that abasic DNA contorts more easily and in specific ways relative to unmodified DNA, an aspect likely to be important in abasic site recognition and hydrolysis.
* To whom correspondence should be addressed. Tel: +1 925 422 1540; Fax: +1 925 424 3130; Email: barsky@llnl.gov
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Curuksu, K. Zakrzewska, and M. Zacharias Magnitude and direction of DNA bending induced by screw-axis orientation: influence of sequence, mismatches and abasic sites Nucleic Acids Res., April 1, 2008; 36(7): 2268 - 2283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, F.-Y. Dupradeau, D. A. Case, C. J. Turner, and J. Stubbe DNA oligonucleotides with A, T, G or C opposite an abasic site: structure and dynamics Nucleic Acids Res., January 17, 2008; 36(1): 253 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Breit, K. Ault-Ziel, A.-B. Al-Mehdi, and M. N. Gillespie Nuclear protein-induced bending and flexing of the hypoxic response element of the rat vascular endothelial growth factor promoter FASEB J, January 1, 2008; 22(1): 19 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Fiala, C. D. Hypes, and Z. Suo Mechanism of Abasic Lesion Bypass Catalyzed by a Y-family DNA Polymerase J. Biol. Chem., March 16, 2007; 282(11): 8188 - 8198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Rieger, E. I. Zaika, W. Xie, F. Johnson, A. P. Grollman, C. R. Iden, and D. O. Zharkov Proteomic Approach to Identification of Proteins Reactive for Abasic Sites in DNA Mol. Cell. Proteomics, May 1, 2006; 5(5): 858 - 867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dash, J. P. Marino, and S. F. J. Le Grice Examining Ty3 Polypurine Tract Structure and Function by Nucleoside Analog Interference J. Biol. Chem., February 3, 2006; 281(5): 2773 - 2783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Nakano, Y. Uotani, K. Uenishi, M. Fujii, and N. Sugimoto DNA base flipping by a base pair-mimic nucleoside Nucleic Acids Res., December 15, 2005; 33(22): 7111 - 7119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. G. Beloglazova, O. O. Kirpota, K. V. Starostin, A. A. Ishchenko, V. I. Yamkovoy, D. O. Zharkov, K. T. Douglas, and G. A. Nevinsky Thermodynamic, kinetic and structural basis for recognition and repair of abasic sites in DNA by apurinic/apyrimidinic endonuclease from human placenta Nucleic Acids Res., September 30, 2004; 32(17): 5134 - 5146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Guliaev, B. Hang, and B. Singer Structural insights by molecular dynamics simulations into specificity of the major human AP endonuclease toward the benzene-derived DNA adduct, pBQ-C Nucleic Acids Res., May 20, 2004; 32(9): 2844 - 2852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Somoza, D. Andreatta, C. J. Murphy, R. S. Coleman, and M. A. Berg Effect of lesions on the dynamics of DNA on the picosecond and nanosecond timescales using a polarity sensitive probe Nucleic Acids Res., May 6, 2004; 32(8): 2494 - 2507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. V. Koval, N. A. Kuznetsov, D. O. Zharkov, A. A. Ishchenko, K. T. Douglas, G. A. Nevinsky, and O. S. Fedorova Pre-steady-state kinetics shows differences in processing of various DNA lesions by Escherichia coli formamidopyrimidine-DNA glycosylase Nucleic Acids Res., February 9, 2004; 32(3): 926 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Giudice, P. Varnai, and R. Lavery Base pair opening within B-DNA: free energy pathways for GC and AT pairs from umbrella sampling simulations Nucleic Acids Res., March 1, 2003; 31(5): 1434 - 1443. [Abstract] [Full Text] [PDF]
|
|