Redox regulation of the DNA repair function of the human AP endonuclease Ape1/ref-1

Mark Kelley, S. H. Parsons

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

The second enzyme in the DNA base excision repair (BER) pathway, apurinic/apyrimidinic (AP) endonuclease or Ape1, hydrolyzes the phosphodiester backbone immediately 5′ to an AP site generating a normal 3′-hydroxyl group and an abasic deoxyribose-5-phosphate, which is processed by subsequent enzymes of the BER pathway. AP sites are the most common form of DNA damage, and the persistence of AP sites in DNA results in a block to DNA replication, cytotoxic mutations, and genetic instability. Interestingly, Ape1/ref-1 is a multifunctional protein that not only is a DNA repair enzyme, but also functions as a redox factor maintaining transcription factors, such as Fos, Jun, nuclear factor-κB, PAX (paired box-containing family of genes), hypoxia inducible factor-1α (HIF-1α), HIT-1-like factor, and p53, in an active reduced state. Ape1/ref-1 has also been implicated in a number of other activities, one of which is the activation of bioreductive drugs requiring reduction for activity. In this report, we present data supporting our findings that another level of posttranslational modification of Ape1/ref-1 that clearly affects the AP endonuclease activity is the reduction or oxidation of this protein. Furthermore, we show data demonstrating that at least one of the sites involved in this redox regulation is the cysteine amino acid found at position 310, immediately adjacent to the crucial histidine residue at position 309 in the DNA repair active site. These findings suggest that the Ape1/ref-1 protein may be much more intimately regulated at the posttranslational level than initially imagined.

Original languageEnglish
Pages (from-to)671-683
Number of pages13
JournalAntioxidants and Redox Signaling
Volume3
Issue number4
StatePublished - 2001

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Endonucleases
DNA Repair
Oxidation-Reduction
Repair
DNA
DNA-(Apurinic or Apyrimidinic Site) Lyase
DNA Repair Enzymes
Deoxyribose
Hypoxia-Inducible Factor 1
Proteins
Enzymes
Post Translational Protein Processing
DNA Replication
Histidine
Hydroxyl Radical
Thermodynamic properties
DNA Damage
Cysteine
Catalytic Domain
Transcription Factors

ASJC Scopus subject areas

  • Biochemistry

Cite this

Redox regulation of the DNA repair function of the human AP endonuclease Ape1/ref-1. / Kelley, Mark; Parsons, S. H.

In: Antioxidants and Redox Signaling, Vol. 3, No. 4, 2001, p. 671-683.

Research output: Contribution to journalArticle

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