title: Human apurinic/apyrimidinic endonuclease 1.
abstract: CONCLUSIONS
  Human apurinic/apyrimidinic endonuclease 1 (APE1, also known as REF-1) was isolated based on its ability to cleave at AP sites in DNA or activate the DNA binding activity of certain transcription factors. We review herein topics related to this multi-functional DNA repair and stress-response protein.
  
  
  BACKGROUND
  APE1 displays homology to Escherichia coli exonuclease III and is a member of the divalent metal-dependent α/β fold-containing phosphoesterase superfamily of enzymes. APE1 has acquired distinct active site and loop elements that dictate substrate selectivity, and a unique N-terminus which at minimum imparts nuclear targeting and interaction specificity. Additional activities ascribed to APE1 include 3'-5' exonuclease, 3'-repair diesterase, nucleotide incision repair, damaged or site-specific RNA cleavage, and multiple transcription regulatory roles.
  
  
  RESULTS
  APE1 is essential for mouse embryogenesis and contributes to cell viability in a genetic background-dependent manner. Haploinsufficient APE1(+/-) mice exhibit reduced survival, increased cancer formation, and cellular/tissue hyper-sensitivity to oxidative stress, supporting the notion that impaired APE1 function associates with disease susceptibility. Although abnormal APE1 expression/localization has been seen in cancer and neuropathologies, and impaired-function variants have been described, a causal link between an APE1 defect and human disease remains elusive.
  
  
  CONCLUSIONS
  Ongoing efforts aim at delineating the biological role(s) of the different APE1 activities, as well as the regulatory mechanisms for its intra-cellular distribution and participation in diverse molecular pathways. The determination of whether APE1 defects contribute to human disease, particularly pathologies that involve oxidative stress, and whether APE1 small-molecule regulators have clinical utility, is central to future investigations.
authors.affiliation: Intramural Research Program, Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health , Baltimore, Maryland.
authors.forename: Mengxia
authors.initials: M
authors.lastname: Li
authors.forename: David M
authors.initials: DM
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D020134:Catalytic Domain; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D058990:Molecular Targeted Therapy; D020125:Mutation, Missense; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D017433:Protein Structure, Secondary; D059367:RNA Cleavage
chemical_list: D000970:Antineoplastic Agents; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase