Nuclear magnetic resonance investigation of primer-template models: Formation, of a pyrimidine bulge upon misincorporation
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AbstractOur previous studies have shown that misaligned structures can occur upon misincorporation of a dNTP opposite thymine templates. The formation of misaligned structures during DNA replication, if not repaired properly, can be bypassed and extended by low-fidelity polymerases and ultimately lead to mutations. In this study, the base pair structures at the replicating sites of a set of primer-template models which mimic the situation upon misincorporation of a dNTP opposite cytosine templates have been determined. High-resolution NMR structural results show that misaligned structures with a C-bulge can be formed upon incorporation of dCTP, dTTP, and dATP opposite 5'-GC, 5'-AC, and 5'-TC templates, respectively. The stabilities of misaligned structures depend on the types of terminal base pairs at the replicating sites. Together with the structural findings in thymine templates, we conclude that terminal G-C and C-G base pairs always contribute a larger stabilizing effect to the misaligned structures containing a pyrimidine bulge than terminal A center dot T and T center dot A base pairs. Misalignment and thus deletion mutation are more likely to occur if misincorporation of a nucleotide opposite a pyrimidine template can cause template slippage to form a terminal G-C or C-G base pair. Although misalignment also occurs when the newly formed terminal base pair is an A-T base pair or a T-A base pair, both misaligned and mismatched conformers coexist, which can lead to deletion and substitution mutations, respectively.
All Author(s) ListChi LM, Lam SL
Journal nameBiochemistry
Year2008
Month4
Day15
Volume Number47
Issue Number15
PublisherAmerican Chemical Society
Pages4469 - 4476
ISSN0006-2960
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY

Last updated on 2021-15-09 at 01:12