Title: Direct observation of 2 base-pairing modes of a cytosine-thymine analog with guanine in a dna z-form duplex - significance for base analog mutagenesis
Authors: Moore, Mh ×
Van Meervelt, Luc
Sallisbury, Sa
Lin, Pkt
Brown, Dm #
Issue Date: Jan-1995
Publisher: Academic press (london) ltd
Series Title: Journal of Molecular Biology vol:251 issue:5 pages:665-673
Abstract: The pyrimidine nucleobase analogue 6H,8H-3,4-dihydropyrimido[4,5-c][1,2]oxazin-7-one (P) is a mimic both of cytosine and thymine, since it can form stable hydrogen-bonded base-pairs with either guanine or adenine. To investigate the geometric properties of pairing with guanine in a DNA double helix, the structure of d(CGCGPG)2 has been determined by single crystal X-ray analysis. The oligonucleotide crystallised as a left-handed Z-DNA duplex in the orthorhombic space group P2(1)2(1)2(1) With cell dimensions a = 18.23 Angstrom, b = 30.63 Angstrom, c = 43.78 Angstrom. Refinement using NUCLSQ with 51 water molecules included in the final model converged at R = 0.179 (R(w) = 0.159) for 2798 reflections (F > 2 sigma(F)) in the range 8 Angstrom to 1.7 Angstrom. Remarkably, the two P . G pairs in the hexamer duplex are different: Watson-Crick and wobble types separately illustrate both cytosine-like and thymine-like behaviour. The result suggests that mutagenesis experiments involving P and other analogues which display pronounced base-pairing ambivalence can be used to examine the structural basis of substrate discrimination by polymerases that is essential to accurate genetic replication. (C) 1995 Academic Press Limited
ISSN: 0022-2836
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Biochemistry, Molecular and Structural Biology Section
× corresponding author
# (joint) last author

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