Going APE over ref-1

The DNA base excision repair (BER) pathway is responsible for the repair of cellular alkylation and oxidative DNA damage. A crucial and the second ste p in the BER pathway involves the cleavage of baseless sites in DNA by an A P endonuclease. The major AP endonuclease in mammalian cells is Ape1/ref-1. Ape1/ref-1 is a multifunctional protein that is not only responsible for r epair of AP sites, but also functions as a reduction-oxidation (redox) fact or maintaining transcription factors in an active reduced state. Ape1/ref-1 has been shown to stimulate the DNA binding activity of numerous transcrip tion factors that are involved in cancer promotion and progression such as Fos, Jun, NF(B, PAX, HIF-1(, HLF and p53. Ape1/ref-1 has also been implicat ed in the activation of bioreductive drugs which require reduction in order to be active and has been shown to interact with a subunit of the Ku antig en to act as a negative regulator of the parathyroid hormone promoter, as w ell as part of the HREBP transcription factor complex. Ape1/ref-1 levels ha ve been found to be elevated in a number of cancers such as ovarian, cervic al, prostate, rhabdomyosarcomas and germ cell tumors and correlated with th e radiosensitivity of cervical cancers. In this review, we have attempted t o try and assimilated as much data concerning Ape1/ref-1 and incorporate th e rapidly growing information oh Ape1/ref-1 in a wide variety of functions and systems. (C) 2000 Elsevier Science B.V. All rights reserved.