Increasing occurrences and functional roles for high energy purine-pyrimidine base-pairs in nucleic acids

There are a growing number of studies reporting the observation of purine-pyrimidine base-pairs that are seldom observed in unmodified nucleic acids because they entail the loss of energetically favorable interactions or require energetically costly base ionization or tautomerization. These high energy purine-pyrimidine base-pairs include G center dot C+ and A center dot T Hoogsteen base-pairs, which entail 1800 rotation of the purine base in a Watson-Crick base-pair, protonation of cytosine N3, and constriction of the C1 '-C1 ' distance by similar to 2.5 angstrom. Other high energy pure-pyrimidine base-pairs include G center dot T, G center dot U, and A center dot C mispairs that adopt Watson-Crick like geometry through either base ionization or tautomerization. Although difficult to detect and characterize using biophysical methods, high energy purine-pyrimidine base-pairs appear to be more common than once thought. They further expand the structural and functional diversity of canonical and non-canonical nucleic acid base-pairs.