Replication across Template T/U by Human DNA Polymerase
Human DNA polymerase (Pol) 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 Pol 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 Pol 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 Pol.
- Research Organization:
- Argonne National Laboratory (ANL)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1006155
- Journal Information:
- Structure, Journal Name: Structure Journal Issue: (7) ; 07, 2009 Vol. 17
- Country of Publication:
- United States
- Language:
- ENGLISH
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