Replication across Template T/U by Human DNA Polymerase-ι

Rinku Jain, Deepak T. Nair, Robert E. Johnson, Louise Prakash, Satya Prakash, Aneel K. Aggarwal

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Human DNA polymerase-ι (Polι) 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 Polι 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 Polι 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 Polι.

Original languageEnglish (US)
Pages (from-to)974-980
Number of pages7
JournalStructure
Volume17
Issue number7
DOIs
StatePublished - Jul 15 2009

Keywords

  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

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