DNA polymerase 3'→5' exonuclease activity: Different roles of the beta hairpin structure in family-B DNA polymerases

DNA Repair
Hariyanto DarmawanLinda J Reha-Krantz

Abstract

Proofreading by the bacteriophage T4 and RB69 DNA polymerases requires a β hairpin structure that resides in the exonuclease domain. Genetic, biochemical and structural studies demonstrate that the phage β hairpin acts as a wedge to separate the primer-end from the template strand in exonuclease complexes. Single amino acid substitutions in the tip of the hairpin or deletion of the hairpin prevent proofreading and create "mutator" DNA polymerases. There is little known, however, about the function of similar hairpin structures in other family B DNA polymerases. We present mutational analysis of the yeast (Saccharomyces cerevisiae) DNA polymerase δ hairpin. Deletion of the DNA polymerase δ hairpin (hpΔ) did not significantly reduce DNA replication fidelity; thus, the β hairpin structure in yeast DNA polymerase δ is not essential for proofreading. However, replication efficiency was reduced as indicated by a slow growth phenotype. In contrast, the G447D amino acid substitution in the tip of the hairpin increased frameshift mutations and sensitivity to hydroxyurea (HU). A chimeric yeast DNA polymerase δ was constructed in which the T4 DNA polymerase hairpin (T4hp) replaced the yeast DNA polymerase δ hairpin; a strong increase in f...Continue Reading

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Citations

Sep 22, 2016·Nucleic Acids Research·Claudia HuberAndreas Marx
Feb 6, 2017·Virus Research·Karima ZarroukGuy Boivin
Oct 19, 2017·Nucleic Acids Research·Céline RalecGhislaine Henneke
Feb 28, 2019·Journal of Molecular Modeling·M C FoleyA Boyke
Mar 4, 2018·Current Genetics·Anna Bębenek, Izabela Ziuzia-Graczyk

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