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

• Published in: Cancer research (Chicago, Ill.) Ill.), 1997-12, Vol.57 (24), p.5457-5459
• Main Authors: YACOUB, A, KELLEY, M. R, DEUTSCH, W. A
• Format: Article
• Language: English
• Subjects: Binding Sites; Biological and medical sciences; Carbon-Oxygen Lyases - metabolism; Casein Kinase II; Casein Kinases; Deoxyribonuclease IV (Phage T4-Induced); DNA - metabolism; DNA Repair - physiology; DNA-(Apurinic or Apyrimidinic Site) Lyase; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Humans; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Nuclear Proteins - metabolism; Phosphorylation; Protein Kinases - metabolism; Protein-Serine-Threonine Kinases - metabolism
• ISSN: 0008-5472; 1538-7445

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.