NMR investigation of DNA primer-template models: guanine templates are less prone to strand slippage upon misincorporation.
Misaligned structures can result from strand slippage during DNA replication and, if not repaired, would lead to mutations. Previously, we showed that strand slippage can occur upon misincorporation of a dNTP opposite thymine and cytosine templates, resulting in a misaligned structure with a T- or C-bulge. The formation propensity for misaligned structures was found to depend on the type of terminal base pair. In this study, we performed NMR investigations on primer-template models containing a guanine template. Our results reveal guanine templates are less prone to strand slippage than pyrimidine templates. Misalignment was found to occur only in 5'-CG templates with a downstream purine. In addition to the significance of terminal base pair and upstream nucleotide, the present study reveals the importance of the templating base and its downstream nucleotide, which also determine the propensity of strand slippage in primer-templates.
Chi
Lai Man
LM
Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Lam
Sik Lok
SL
D020029:Base Pairing; D003596:Cytosine / Q000737:chemistry; D004249:DNA Damage / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry* / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D006147:Guanine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011743:Pyrimidines / Q000737:chemistry; D013698:Templates, Genetic
D017931:DNA Primers; D011743:Pyrimidines; D006147:Guanine; D003596:Cytosine; C030986:pyrimidine