Intracellular trafficking and regulation of mammalian AP-endonuclease 1 (APE1), an essential DNA repair protein
- 作者：Sankar Mitra ; Tadahide Izumi ; Istvan Boldogh ; Kishor K. Bhakat ; Ranajoy Chattopadhyay ; Bartosz Szczesny
- 关键词：Nuclear export signal ; Age-dependent repair activity ; Mitochondrial APE ; Spontaneous AP sites
- 刊名：DNA Repair
- 出版年：2007
- 期刊代码：121_15687864
- 类别：ch
- 出版时间：1 April 2007
- 卷：6
- 期：4
- 页码：461-469
- 文件大小：553 K
摘要
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.