Abasic sites in duplex DNA: Molecular modeling of sequence-dependent effects on conformation

被引:37
作者
Ayadi, L
Coulombeau, C
Lavery, R
机构
[1] Univ Grenoble 1, LEDSS, Chim Bioorgan Lab, UMR CNRS 5616, F-38041 Grenoble 9, France
[2] Inst Biol Physicochim, Lab Biochim Theor, F-75005 Paris, France
基金
澳大利亚研究理事会;
关键词
D O I
10.1016/S0006-3495(99)77152-3
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Molecular modeling calculations using Junction Minimization of Nucleic Acids (JUMNA) have been used to study sequence effects on the conformation of abasic sites within duplex DNA. We have considered lesions leading to all possible unpaired bases (X), adenine, guanine, cytosine, or thymine contained within two distinct sequence contexts, CXC and GXG. Calculations were carried out on DNA 11-mers using extensive conformational search techniques to locate the most stable abasic conformations and using Poisson-Boltzmann corrected electrostatics to account for solvation effects. The results, which are in very good agreement with available experimental data, point to strong sequence effects on both the position of the unpaired base (intra or extrahelical) and on the overall curvature induced by the abasic lesion. For CXC, unpaired purines are found to lie within the helix, while unpaired pyrimidines are either extrahelical or in equilibrium between the intra and extrahelical forms. For GXG, all unpaired bases lead to intrahelical forms, but with marked, sequence-dependent differences in induced curvature.
引用
收藏
页码:3218 / 3226
页数:9
相关论文
共 54 条
[1]   LEFT-HANDED DNA HELICES [J].
ARNOTT, S ;
CHANDRASEKARAN, R ;
BIRDSALL, DL ;
LESLIE, AGW ;
RATLIFF, RL .
NATURE, 1980, 283 (5749) :743-745
[2]  
Ayadi L, 1997, BIOLOGICAL MACROMOLECULAR DYNAMICS, P83
[3]  
AYADI L, 1999, IN PRESS J BIOMOL ST
[4]   STRUCTURE AND FUNCTION OF APURINIC/APYRIMIDINIC ENDONUCLEASES [J].
BARZILAY, G ;
HICKSON, ID .
BIOESSAYS, 1995, 17 (08) :713-719
[5]   Modelling base pair opening: the role of helical twist [J].
Bernet, J ;
Zakrzewska, K ;
Lavery, R .
JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 1997, 398 :473-482
[6]   CODING PROPERTIES OF POLY(DEOXYCYTIDYLIC ACID) TEMPLATES CONTAINING URACIL OR APYRIMIDINIC SITES - INVITRO MODULATION OF MUTAGENESIS BY DEOXYRIBONUCLEIC-ACID REPAIR ENZYMES [J].
BOITEUX, S ;
LAVAL, J .
BIOCHEMISTRY, 1982, 21 (26) :6746-6751
[7]   Solution conformation of an abasic DNA undecamer duplex d(CGCACXCACGC)-d(GCGTGTGTGCG): The unpaired thymine stacks inside the helix [J].
Coppel, Y ;
Berthet, N ;
Coulombeau, C ;
Coulombeau, C ;
Garcia, J ;
Lhomme, J .
BIOCHEMISTRY, 1997, 36 (16) :4817-4830
[8]   ABASIC FRAMESHIFT IN DNA - SOLUTION CONFORMATION DETERMINED BY PROTON NMR AND MOLECULAR MECHANICS CALCULATIONS [J].
CUNIASSE, P ;
SOWERS, LC ;
ERITJA, R ;
KAPLAN, B ;
GOODMAN, MF ;
COGNET, JAH ;
LEBRET, M ;
GUSCHLBAUER, W ;
FAZAKERLEY, GV .
BIOCHEMISTRY, 1989, 28 (05) :2018-2026
[9]   AN ABASIC SITE IN DNA - SOLUTION CONFORMATION DETERMINED BY PROTON NMR AND MOLECULAR MECHANICS CALCULATIONS [J].
CUNIASSE, P ;
SOWERS, LC ;
ERITJA, R ;
KAPLAN, B ;
GOODMAN, MF ;
COGNET, JAH ;
LEBRET, M ;
GUSCHLBAUER, W ;
FAZAKERLEY, GV .
NUCLEIC ACIDS RESEARCH, 1987, 15 (19) :8003-8022
[10]   THE ABASIC SITE AS A CHALLENGE TO DNA-POLYMERASE - A NUCLEAR-MAGNETIC-RESONANCE STUDY OF G, C AND T OPPOSITE A MODEL ABASIC SITE [J].
CUNIASSE, P ;
FAZAKERLEY, GV ;
GUSCHLBAUER, W ;
KAPLAN, BE ;
SOWERS, LC .
JOURNAL OF MOLECULAR BIOLOGY, 1990, 213 (02) :303-314