The active site of high-fidelity DNA polymerase is only able to accommodate Watson-Crick base pairing, due to it having a highly specific structure. However, where an error is incorporated into the DNA strand, a trans-lesion DNA polymerase may be used. This has a wider, more forgiving active site, allowing for alternative base pairing to occur (such as Hoogsteen pairing).
Due to the highly constricted nature of the DNA polymerase active site, it is very uncommon for alternative base pairing to occur. Hoogsteen base pairing is still between A and T, G and C, but the bases are rotated, giving a different conformation in the DNA structure. This was first observed in X-ray crystal structures about 10 years after Watson, Crick, and Franklin identified the structure of DNA.