TY - JOUR
T1 - Intracellular trafficking and regulation of mammalian AP-endonuclease 1 (APE1), an essential DNA repair protein
AU - Mitra, Sankar
AU - Izumi, Tadahide
AU - Boldogh, Istvan
AU - Bhakat, Kishor K.
AU - Chattopadhyay, Ranajoy
AU - Szczesny, Bartosz
N1 - Funding Information:
The original research described in this review was supported by USPHS R01 ES08457, R01 CA53791 (SM), P30 ES06676, P01 AG-21803 (IB, SM), R01 CA98664 (TI). We express our sincere gratitude to Xiao-Feng Qin (M.D. Anderson Cancer Center, Houston, TX) for providing the lentiviral vector and critical guidance for generating recombinant lentiviruses. We also thank Wanda Smith for expert secretarial assistance and UTMB Cell Sorting Facility for FACS analysis.
PY - 2007/4/1
Y1 - 2007/4/1
N2 - 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.
AB - 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.
KW - Age-dependent repair activity
KW - Mitochondrial APE
KW - Nuclear export signal
KW - Spontaneous AP sites
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U2 - 10.1016/j.dnarep.2006.10.010
DO - 10.1016/j.dnarep.2006.10.010
M3 - Article
C2 - 17166779
AN - SCOPUS:33847666362
SN - 1568-7864
VL - 6
SP - 461
EP - 469
JO - DNA Repair
JF - DNA Repair
IS - 4
ER -