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Review
. 2007 Dec;11(6):588-94.
doi: 10.1016/j.cbpa.2007.09.019. Epub 2007 Nov 9.

Model systems for understanding DNA base pairing

Andrew T Krueger  1 , Eric T Kool
Affiliations
Review

Model systems for understanding DNA base pairing

Andrew T Krueger et al. Curr Opin Chem Biol. 2007 Dec.

Abstract

The fact that nucleic acid bases recognize each other to form pairs is a canonical part of the dogma of biology. However, they do not recognize each other well enough in water to account for the selectivity and efficiency that is needed in the transmission of biological information through a cell. Thus proteins assist in this recognition in multiple ways, and recent data suggest that these mechanisms of recognition can vary widely with context. To probe how the chemical differences of the four nucleobases are defined in various biological contexts, chemists and biochemists have developed modified versions that differ in their polarity, shape, size, and functional groups. This brief review covers recent advances in this field of research.

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Figures

Figure 1
Figure 1
Varied depictions of the four natural DNA bases, showing differences in size, shape, electrostatics, and functional groups. The chemical information of the cell is defined by these differences.
Figure 2
Figure 2
The consensus base pair shape. Space-filling models of the four common pairs (with sugars attached) are overlaid. Darkest green color indicates space that is occupied by all four, while lightest areas show variations that project outward.
Figure 3
Figure 3
The strong effect of systematic changes in base size on the fidelity of replication in Escherichia coli. Thymine analogs varied in size over a 1 Å range, and were found to be replaced by the bases shown after replication. Data from Kim et al. [2].
Figure 4
Figure 4
Representative examples from the menagerie of modified DNA bases in the literature, showing the wide range of structures, sizes, shapes, and polarities.
See this image and copyright information in PMC

References

    1. Kim TW, Kool ET. A series of nonpolar thymine analogues of increasing size: DNA base pairing and stacking properties. J Org Chem. 2005;70:2048–2053. - PubMed
    1. Kim TW, Delaney JC, Essigmann JM, Kool ET. Probing the active site tightness of DNA polymerase in sub-angstrom increments. Proc Natl Acad Sci USA. 2005;102:15803–15808. A systematic study of steric effects on replication, carried out both in vitro and in living bacteria. - PMC - PubMed
    1. Kim TW, Brieba LG, Ellenberger T, Kool ET. Functional evidence for a small and rigid active site in a high fidelity DNA polymerase: probing T7 DNA polymerase with variably sized base pairs. J Biol Chem. 2006;281:2289–2295. - PubMed
    1. Hirao I, Kimoto M, Mitsui T, Fujiwara T, Kawai R, Sato A, Harada Y, Yokoyama S. An unnatural hydrophobic base pair system: site-specific incorporation of nucleotide analogs into DNA and RNA. Nat Methods. 2006;9:729–735. - PubMed
    1. Mitsui T, Kimoto M, Harada Y, Yokoyama S, Hirao I. An efficient unnatural base pair for a base-pair-expanded transcription system. J Am Chem Soc. 2005;127:8652–8658. A particularly effective example of a nonnatural, non-hydrogen-bonded base pair that is a substrate for polymerases. It is has been shown to have useful applications in labeling RNAs. - PubMed

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