An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3′ mispaired DNA
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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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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Characterization of the Endoribonuclease Active Site of Human Apurinic/Apyrimidinic Endonuclease 1
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A new perspective on oxidation of DNA repair proteins and cancer
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Disparity between DNA base excision repair in yeast and mammals: translational implications.
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Endoribonucleases – enzymes gaining spotlight in mRNA metabolism
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Structural basis for overhang excision and terminal unwinding of DNA duplexes by TREX1
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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
- Licence
- www.springer.com/tdm (tdm)
- 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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