Intracellular trafficking and regulation of mammalian AP-endonuclease 1 (APE1), an essential DNA repair protein.
AP endonuclease (APE), with dual activities as an endonuclease and a 3' exonuclease, is a central player in repair of oxidized and alkylated bases in the genome via the base excision repair (BER) pathway. APE acts as an endonuclease in repairing AP sites generated spontaneously or after base excision during BER. It also removes the 3' blocking groups in DNA generated directly by ROS or after AP lyase reaction. In contrast to E. coli and lower eukaryotes which express two distinct APEs of Xth and Nfo types, mammalian genomes encode only one APE, APE1, which is of the Xth type. However, while the APEs together are dispensable in the bacteria and simple eukaryotes, APE1 is essential for mammalian cells. We have shown that apoptosis of mouse embryo fibroblasts triggered by APE1 inactivation can be prevented by ectopic expression of repair competent but not repair-defective APE1. The mitochondrial APE (mtAPE) is an N-terminal truncation product of APE1. A significant fraction of APE1 is cytosolic, and oxidative stress induces its nuclear and mitochondrial translocation. Such age-dependent increase in APE activity in the nucleus and mitochondria is consistent with the hypothesis that aging is associated with chronic oxidative stress.
Mitra
Sankar
S
Sealy Center for Molecular Science and Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA. samitra@utmb.edu
Izumi
Tadahide
T
Boldogh
Istvan
I
Bhakat
Kishor K
KK
Chattopadhyay
Ranajoy
R
Szczesny
Bartosz
B
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology / Q000648:ultrastructure; D008322:Mammals; D051379:Mice; D010084:Oxidation-Reduction; D021381:Protein Transport
C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase