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The mechanism of the translocation step in DNA replication by DNA polymerase I: a computer simulation analysis.

Publication ,  Journal Article
Golosov, AA; Warren, JJ; Beese, LS; Karplus, M
Published in: Structure
January 13, 2010

High-fidelity DNA polymerases copy DNA rapidly and accurately by adding correct deoxynucleotide triphosphates to a growing primer strand of DNA. Following nucleotide incorporation, a series of conformational changes translocate the DNA substrate by one base pair step, readying the polymerase for the next round of incorporation. Molecular dynamics simulations indicate that the translocation consists globally of a polymerase fingers-opening transition, followed by the DNA displacement and the insertion of the template base into the preinsertion site. They also show that the pyrophosphate release facilitates the opening transition and that the universally conserved Y714 plays a key role in coupling polymerase opening to DNA translocation. The transition involves several metastable intermediates in one of which the O helix is bent in the vicinity of G711. Completion of the translocation appears to require a gating motion of the O1 helix, perhaps facilitated by the presence of G715. These roles are consistent with the high level of conservation of Y714 and the two glycine residues at these positions. It is likely that a corresponding mechanism is applicable to other polymerases.

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Published In

Structure

DOI

EISSN

1878-4186

Publication Date

January 13, 2010

Volume

18

Issue

1

Start / End Page

83 / 93

Location

United States

Related Subject Headings

  • Substrate Specificity
  • Protein Structure, Tertiary
  • Nucleic Acid Conformation
  • Molecular Dynamics Simulation
  • Diphosphates
  • DNA Replication
  • DNA Polymerase I
  • DNA
  • Crystallography, X-Ray
  • Biophysics
 

Citation

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Golosov, A. A., Warren, J. J., Beese, L. S., & Karplus, M. (2010). The mechanism of the translocation step in DNA replication by DNA polymerase I: a computer simulation analysis. Structure, 18(1), 83–93. https://doi.org/10.1016/j.str.2009.10.014
Golosov, Andrei A., Joshua J. Warren, Lorena S. Beese, and Martin Karplus. “The mechanism of the translocation step in DNA replication by DNA polymerase I: a computer simulation analysis.Structure 18, no. 1 (January 13, 2010): 83–93. https://doi.org/10.1016/j.str.2009.10.014.
Golosov AA, Warren JJ, Beese LS, Karplus M. The mechanism of the translocation step in DNA replication by DNA polymerase I: a computer simulation analysis. Structure. 2010 Jan 13;18(1):83–93.
Golosov, Andrei A., et al. “The mechanism of the translocation step in DNA replication by DNA polymerase I: a computer simulation analysis.Structure, vol. 18, no. 1, Jan. 2010, pp. 83–93. Pubmed, doi:10.1016/j.str.2009.10.014.
Golosov AA, Warren JJ, Beese LS, Karplus M. The mechanism of the translocation step in DNA replication by DNA polymerase I: a computer simulation analysis. Structure. 2010 Jan 13;18(1):83–93.

Published In

Structure

DOI

EISSN

1878-4186

Publication Date

January 13, 2010

Volume

18

Issue

1

Start / End Page

83 / 93

Location

United States

Related Subject Headings

  • Substrate Specificity
  • Protein Structure, Tertiary
  • Nucleic Acid Conformation
  • Molecular Dynamics Simulation
  • Diphosphates
  • DNA Replication
  • DNA Polymerase I
  • DNA
  • Crystallography, X-Ray
  • Biophysics