Human DNA polymerase-iota (Poliota) incorporates correct nucleotides opposite template purines with a much higher efficiency and fidelity than opposite template pyrimidines. In fact, the fidelity opposite template T is so poor that Poliota inserts an incorrect dGTP approximately 10 times better than it inserts the correct dATP. We determine here how a template T/U is accommodated in the Poliota active site and why a G is incorporated more efficiently than an A. We show that in the absence of incoming dATP or dGTP (binary complex), template T/U exists in both syn and anti conformations, but in the presence of dATP or dGTP (ternary complexes), template T/U is predominantly in the anti conformation. We also show that dATP and dGTP insert differently opposite template T/U, and that the basis of selection of dGTP over dATP is a hydrogen bond between the N2 amino group of dGTP and Gln59 of Poliota.
Replication across template T/U by human DNA polymerase-iota.,Jain R, Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK Structure. 2009 Jul 15;17(7):974-80. PMID:19604477
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↑ Jain R, Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK. Replication across template T/U by human DNA polymerase-iota. Structure. 2009 Jul 15;17(7):974-80. PMID:19604477 doi:S0969-2126(09)00216-0