The DNA repair activity of human redox/repair protein APE/Ref-1 is inactivated by phosphorylation

Adly Yacoub, Mark Kelley, Walter A. Deutsch

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

The human DNA repair protein apurinic/apyrimidinic endonuclease (APE) is a dual-function protein that has important roles in both the repair of baseless sites that arise in DNA and in regulating the redox state of a number of proteins (Ref-1). Although previous attention has been focused on how the human APE/Ref-1 gene may be regulated at the DNA level, we have instead examined if APE/Ref-1 is phosphorylated, and if so how it may affect DNA repair activity. We demonstrate here that APE/Ref-1 is indeed a substrate for phosphorylation by the serine/threonine casein kinases (CK) I and II and protein kinase C. Notably, although phosphorylation by CKI and protein kinase C had no effect whatsoever on the ability of APE/Ref-1 to act at abasic sites in DNA, phosphorylation by CKII completely abolished DNA repair activity. That phosphorylation was responsible for the loss of abasic repair activity was concluded from experiments showing that inactive APE/Ref-1 could be reversed to an active DNA repair protein with phosphatase treatment. These results may help to explain the mechanism by which APE/Ref-1 switches from one unrelated function to another.

Original languageEnglish
Pages (from-to)5457-5459
Number of pages3
JournalCancer Research
Volume57
Issue number24
StatePublished - Dec 15 1997

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Endonucleases
Human Activities
DNA Repair
Oxidation-Reduction
Phosphorylation
Proteins
Protein Kinase C
DNA
Cyclin-Dependent Kinase Inhibitor Proteins
Casein Kinase I
DNA-(Apurinic or Apyrimidinic Site) Lyase
Casein Kinase II
Phosphoprotein Phosphatases
Protein-Serine-Threonine Kinases
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The DNA repair activity of human redox/repair protein APE/Ref-1 is inactivated by phosphorylation. / Yacoub, Adly; Kelley, Mark; Deutsch, Walter A.

In: Cancer Research, Vol. 57, No. 24, 15.12.1997, p. 5457-5459.

Research output: Contribution to journalArticle

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