Intracellular trafficking and regulation of mammalian AP-endonuclease 1 (APE1), an essential DNA repair protein

Sankar Mitra, Tadahide Izumi, Istvan Boldogh, Kishor K. Bhakat, Ranajoy Chattopadhyay, Bartosz Szczesny

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)461-469
Number of pages9
JournalDNA Repair
Volume6
Issue number4
DOIs
StatePublished - Apr 1 2007

Fingerprint

DNA-(Apurinic or Apyrimidinic Site) Lyase
Transcription Factor AP-1
DNA Repair
Repair
DNA
Proteins
spleen exonuclease
Oxidative stress
Endonucleases
Eukaryota
Oxidative Stress
Genes
Genome
Mitochondria
Fibroblasts
Escherichia coli

Keywords

  • Age-dependent repair activity
  • Mitochondrial APE
  • Nuclear export signal
  • Spontaneous AP sites

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Intracellular trafficking and regulation of mammalian AP-endonuclease 1 (APE1), an essential DNA repair protein. / Mitra, Sankar; Izumi, Tadahide; Boldogh, Istvan; Bhakat, Kishor K.; Chattopadhyay, Ranajoy; Szczesny, Bartosz.

In: DNA Repair, Vol. 6, No. 4, 01.04.2007, p. 461-469.

Research output: Contribution to journalArticle

Mitra, Sankar ; Izumi, Tadahide ; Boldogh, Istvan ; Bhakat, Kishor K. ; Chattopadhyay, Ranajoy ; Szczesny, Bartosz. / Intracellular trafficking and regulation of mammalian AP-endonuclease 1 (APE1), an essential DNA repair protein. In: DNA Repair. 2007 ; Vol. 6, No. 4. pp. 461-469.
@article{7d369062285a4eb690cdf4bd91c212f5,
title = "Intracellular trafficking and regulation of mammalian AP-endonuclease 1 (APE1), an essential DNA repair protein",
abstract = "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.",
keywords = "Age-dependent repair activity, Mitochondrial APE, Nuclear export signal, Spontaneous AP sites",
author = "Sankar Mitra and Tadahide Izumi and Istvan Boldogh and Bhakat, {Kishor K.} and Ranajoy Chattopadhyay and Bartosz Szczesny",
year = "2007",
month = "4",
day = "1",
doi = "10.1016/j.dnarep.2006.10.010",
language = "English (US)",
volume = "6",
pages = "461--469",
journal = "DNA Repair",
issn = "1568-7864",
publisher = "Elsevier",
number = "4",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=33847666362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847666362&partnerID=8YFLogxK

U2 - 10.1016/j.dnarep.2006.10.010

DO - 10.1016/j.dnarep.2006.10.010

M3 - Article

VL - 6

SP - 461

EP - 469

JO - DNA Repair

JF - DNA Repair

SN - 1568-7864

IS - 4

ER -