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New insights into DNA polymerase mechanisms provided by time-lapse crystallography
Journal article   Open access   Peer reviewed

New insights into DNA polymerase mechanisms provided by time-lapse crystallography

Tyler M Weaver, M Todd Washington and Bret D Freudenthal
Current opinion in structural biology, Vol.77, pp.102465-102465
09/26/2022
DOI: 10.1016/j.sbi.2022.102465
PMCID: PMC9772199
PMID: 36174287
url
https://doi.org/10.1016/j.sbi.2022.102465View
Published (Version of record) Open Access

Abstract

DNA polymerases play central roles in DNA replication and repair by catalyzing template-directed nucleotide incorporation. Recently time-lapse X-ray crystallography, which allows one to observe reaction intermediates, has revealed numerous and unexpected mechanistic features of DNA polymerases. In this article, we will examine recent new discoveries that have come from time-lapse crystallography that are currently transforming our understanding of the structural mechanisms used by DNA polymerases. Among these new discoveries are the binding of a third metal ion within the polymerase active site, the mechanisms of translocation along the DNA, the presence of new fidelity checkpoints, a novel pyrophosphatase activity within the active site, and the mechanisms of pyrophosphorolysis.

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