Abstract

Arising from: D. T. Nair, R. E. Johnson, S. Prakash, L. Prakash & A. K. Aggarwal Nature 430, 377–380 (2004); Nair et al. reply.

Human polymerase- belongs to the error-prone Y family of polymerases, which frequently incorporate incorrect nucleotides during DNA replication but can efficiently bypass DNA lesions^{1, 2}. On the basis of X-ray diffraction data, Nair et al. propose that Hoogsteen base-pairing is adopted by DNA during its replication by this enzyme³. Here I re-examine their X-ray data and find that the electron density is very weak for a Hoogsteen base pair formed between a template adenine deoxyribonucleotide in the syn conformation and a deoxythymidine 5'-triphosphate (dTTP), and that the fit is better for a normal Watson–Crick base pair. As a guanine–cytosine (G–C) base pair has no potential to form a Hoogsteen base pair at physiological pH, Hoogsteen base-pairing is unlikely to be used in replication by this polymerase.

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