Two essential but distinct functions of the mammalian abasic endonuclease Academic Article uri icon

Overview

MeSH Major

  • DNA Repair
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Gene Expression Regulation

abstract

  • The mammalian abasic endonuclease, APE1, has two distinct roles in the repair of oxidative DNA damage and in gene regulation. Here we show that both functions are essential for cell survival. Deletion of the APE1 gene causes embryonic lethality in mice, and no nullizygous embryo fibroblasts have been isolated. We have now established nullizygous embryo fibroblast lines from APE1(-/-) mouse embryos that are transgenic with the "floxed" human APE1 (hAPE1) gene. Removal of hAPE1 by Cre expression through nuclear microinjection elicited apoptosis in these cells within 24 h, which was blocked by coinjection of the wild-type hAPE1 gene. In contrast, mutant hAPE1 alleles, lacking either the DNA repair or acetylation-mediated gene regulatory function, could not prevent apoptosis, although the combination of these two mutants complemented APE deficiency induced by Cre. These results indicate that distinct and separable functions of APE1 are both essential for mammalian cells even in vitro and provide the evidence that mammalian cells, unlike yeast or Escherichia coli, absolutely require APE for survival, presumably to protect against spontaneous oxidative DNA damage.

publication date

  • April 19, 2005

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC556297

Digital Object Identifier (DOI)

  • 10.1073/pnas.0500986102

PubMed ID

  • 15824325

Additional Document Info

start page

  • 5739

end page

  • 43

volume

  • 102

number

  • 16