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Cited by 50DNA Repair MechanismsDNA and Nucleic Acid ChemistryBiochemical and Molecular Research

The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.

Hydrolysis of 3'-terminal mispairs in vitro by the 3' .fwdarw. 5' exonuclease of DNA polymerase .delta. permits subsequent extension by DNA polymerase .alpha.

Perrino, Fred W., Loeb, Lawrence A.·1990·Biochemistry

Abstract

Purified DNA polymerase alpha, the major replicating enzyme found in mammalian cells, lacks an associated 3'----5' proofreading exonuclease that, in bacteria, contributes significantly to the accuracy of DNA replication. Calf thymus DNA polymerase alpha cannot remove mispaired 3'-termini, nor can it extend them efficiently. We designed a biochemical assay to search in cell extracts for a putative proofreading exonuclease that might function in concert with DNA polymerase alpha in vivo but dissociates from it during purification. Using this assay, we purified a 3'----5' exonuclease from calf thymus that preferentially hydrolyzes mispaired 3'-termini, permitting subsequent extension of the correctly paired 3'-terminus by DNA polymerase alpha. This exonuclease copurifies with a DNA polymerase activity that is biochemically distinct from DNA polymerase alpha and exhibits characteristics described for a second replicative DNA polymerase, DNA polymerase delta. In related studies, we showed that the 3'----5' exonuclease of authentic DNA polymerase delta, like the purified exonuclease, removes terminal mispairs, allowing extension by DNA polymerase alpha. These data suggest that a single proofreading exonuclease could be shared by DNA polymerases alpha and delta, functioning at the site of DNA replication in mammalian cells.

Overview

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Crossref · 10.1021/bi00474a002

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30 of 30 references verified0 citation errors · 0 not checkable

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Metadata

Authors
Perrino, F. W., & Loeb, L. A.
Affiliations
University of Washington (US)
Venue
Biochemistry
Published
1990-06-05
Volume
29
Issue
22
Pages
5226-5231
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
OpenAlex
W2058420479
Cited by
50
References
30
Citations by year
2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 2 · 2013: 2 · 2012: 1
FWCI
1.43
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r35ca039903-14)
  • National Cancer Institute (T32 CA-09437, T32CA009437, R 35-CA-39903)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords
DNA polymerase delta, 3'-5' exonuclease, proofreading exonuclease, DNA polymerase alpha, DNA replication fidelity, calf thymus
MeSH terms
Animals, Base Sequence, Cattle, DNA Polymerase II, DNA Polymerase III, DNA-Directed DNA Polymerase, Exonucleases, Genetic Techniques, Thymus Gland

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