Crystal structures of a template-independent DNA polymerase: murine terminal deoxynucleotidyltransferase - Institut Pasteur Access content directly
Journal Articles EMBO Journal Year : 2002

Crystal structures of a template-independent DNA polymerase: murine terminal deoxynucleotidyltransferase

M. Delarue
  • Function : Correspondent author
  • PersonId : 840872

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J.B. Boulé
N. Expert-Bezançon
  • Function : Author
N. Jourdan
  • Function : Author
N. Sukumar
  • Function : Author

Abstract

The crystal structure of the catalytic core of murine terminal deoxynucleotidyltransferase (TdT) at 2.35 A resolution reveals a typical DNA polymerase beta-like fold locked in a closed form. In addition, the structures of two different binary complexes, one with an oligonucleotide primer and the other with an incoming ddATP-Co(2+) complex, show that the substrates and the two divalent ions in the catalytic site are positioned in TdT in a manner similar to that described for the human DNA polymerase beta ternary complex, suggesting a common two metal ions mechanism of nucleotidyl transfer in these two proteins. The inability of TdT to accommodate a template strand can be explained by steric hindrance at the catalytic site caused by a long lariat-like loop, which is absent in DNA polymerase beta. However, displacement of this discriminating loop would be sufficient to unmask a number of evolutionarily conserved residues, which could then interact with a template DNA strand. The present structure can be used to model the recently discovered human polymerase mu, with which it shares 43% sequence identity.

Dates and versions

pasteur-04089359 , version 1 (04-05-2023)

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M. Delarue, J.B. Boulé, J. Lescar, N. Expert-Bezançon, N. Jourdan, et al.. Crystal structures of a template-independent DNA polymerase: murine terminal deoxynucleotidyltransferase. EMBO Journal, 2002, 21 (3), pp.427-439. ⟨10.1093/emboj/21.3.427⟩. ⟨pasteur-04089359⟩
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