KARP-1 is induced by DNA damage in a p53- and ataxia telangiectasia mutated-dependent fashion

KARP-1 is induced by DNA damage in a p53- and ataxia telangiectasia mutated-dependent fashion

Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912

Edited by Frederick W. Alt, Harvard Medical School, Boston, MA, and approved April 6, 1998 (received for review October 14, 1997)

Abstract

The KARP-1 (Ku86 Autoantigen Related Protein-1) gene, which is expressed from the human Ku86 autoantigen locus, appears to play a role in mammalian DNA double-strand break repair as a regulator of the DNA-dependent protein kinase complex. Here we demonstrate that KARP-1 gene expression is significantly up-regulated following exposure of cells to DNA damage. KARP-1 mRNA induction was completely dependent on the ataxia telangiectasia and p53 gene products, consistent with the presence of a p53 binding site within the second intron of the KARP-1 locus. These observations link ataxia telangiectasia, p53, and KARP-1 in a common pathway.

Footnotes

↵ * To whom reprint requests should be addressed. e-mail: Eric_Hendrickson{at}brown.edu.
This paper was submitted directly (Track II) to the Proceedings Office.
Abbreviations: AT, ataxia telangiectasia; ATM, AT mutated; DNA-PK, DNA-dependent protein kinase; DSB, double-strand break; RT, reverse transcription.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF039597).