The mechanism of the translocation step in DNA replication by DNA polymerase I: a computer simulation analysis.
Published
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Golosov, AA; Warren, JJ; Beese, LS; Karplus, M
Published Date
- January 13, 2010
Published In
Volume / Issue
- 18 / 1
Start / End Page
- 83 - 93
PubMed ID
- 20152155
Pubmed Central ID
- 20152155
Electronic International Standard Serial Number (EISSN)
- 1878-4186
Digital Object Identifier (DOI)
- 10.1016/j.str.2009.10.014
Language
- eng
Conference Location
- United States