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

Kai Ming Chou, Yung Chi Cheng

Research output: Contribution to journalArticle

172 Citations (Scopus)

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 β (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.

Original languageEnglish (US)
Pages (from-to)655-659
Number of pages5
JournalNature
Volume415
Issue number6872
DOIs
StatePublished - Feb 7 2002
Externally publishedYes

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DNA-(Apurinic or Apyrimidinic Site) Lyase
Human Activities
DNA Repair
DNA
Exodeoxyribonucleases
Deoxyribonucleotides
Exonucleases
Zidovudine
DNA-Directed DNA Polymerase
Nucleosides
Antiviral Agents
HIV
Enzymes

ASJC Scopus subject areas

  • General

Cite this

An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3′ mispaired DNA. / Chou, Kai Ming; Cheng, Yung Chi.

In: Nature, Vol. 415, No. 6872, 07.02.2002, p. 655-659.

Research output: Contribution to journalArticle

Chou, Kai Ming ; Cheng, Yung Chi. / An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3′ mispaired DNA. In: Nature. 2002 ; Vol. 415, No. 6872. pp. 655-659.
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