Cited by 240DNA Repair MechanismsDNA and Nucleic Acid ChemistryHIV/AIDS drug development and treatment

An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3′ mispaired DNA

Chou, Kai-Ming, Cheng, Yung-Chi·2002·Nature

Abstract

Human apurinic/apyrimidinic endonuclease (APE1) is an essential enzyme in DNA base excision repair that cuts the DNA backbone immediately adjacent to the 5' side of abasic sites to facilitate repair synthesis by DNA polymerase beta (ref. 1). Mice lacking the murine homologue of APE1 die at an early embryonic stage. Here we report that APE1 has a DNA exonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules. The efficiency of this activity is inversely proportional to the gap size in DNA. In a base excision repair system reconstituted in vitro, the rejoining of nicked mismatched DNA depended on the presence of APE1, indicating that APE1 may increase the fidelity of base excision repair and may represent a new 3' mispaired DNA repair mechanism. The exonuclease activity of APE1 can remove the anti-HIV nucleoside analogues 3'-azido-3'-deoxythymidine and 2',3'-didehydro-2', 3'-dideoxythymidine from DNA, suggesting that APE1 might have an impact on the therapeutic index of antiviral compounds in this category.

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Crossref · 10.1038/415655a

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  • Although many template-dependent human polymerases lack intrinsic proofreading activity, it is possible that dissociation from DNA after misinsertion may allow proofreading by the exonuclease activity intrinsic to another replication or repair protein, such as Pol δ, Pol ε, or apurinic/apyrimidinic endonuclease.

    “Although many (e.g. at least 10 of 15 template-dependent human) polymerases lack intrinsic proofreading activity (2, 3), it is possible that dissociation from DNA after misinsertion may allow proofreading by the exonuclease activity intrinsic to another replication or repair protein, such as Pol ␦, Pol ⑀, or apurinic/apyrimidinic endonuclease (50).”

    From DNA Replication Fidelity (2004) · cites this paper as [50]

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Authors
Chou, K.-M., & Cheng, Y.-C.
Affiliations
Yale University (US)
Corresponding author
Cheng, Yung-Chi
Venue
Nature
Published
2002-02
Volume
415
Issue
6872
Pages
655-659
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2091521381
Cited by
239
References
26
Citations by year
2026: 1 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 11 · 2021: 9 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 8 · 2015: 3 · 2014: 11 · 2013: 11 · 2012: 7
FWCI
8.00
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
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
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords
apurinic/apyrimidinic endonuclease, APE1, exonuclease activity, base excision repair, DNA mismatch repair, nicked DNA, gapped DNA, DNA repair fidelity, 3'-azido-3'-deoxythymidine
MeSH terms
Cell Line, DNA, DNA Damage, DNA Repair, Exodeoxyribonucleases, Humans, Substrate Specificity, Zidovudine, Stavudine, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Carbon-Oxygen Lyases, DNA-(Apurinic or Apyrimidinic Site) Lyase

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