KARP-1: A novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity

Kyungjae Myung, Dong Ming He, Sang Lee, Eric A. Hendrickson

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The Ku autoantigen plays an integral role in mammalian DNA double-strand break repair as the DNA binding component of the DNA-dependent protein kinase (DNA-PK) complex. Here, we demonstrate that a second gene, KARP-1 (Ku86 Autoantigen Related Protein-1), is expressed from the Ku86 locus. The KARP-1 gene utilizes an upstream promoter and additional exons which results in an extra 9 kDa of protein appended onto the normal Ku86 polypeptide. The KARP-1-specific domain encodes interdigitating hexa- and penta-heptad repeats of leucine residues flanked by a very basic region. Intriguingly, the catalytic subunit of DNA-PK also contains a hexa-heptad repeat of leucines. Consistent with this observation, we observed that human cell lines stably expressing dominant-negative constructs of KARP-1 resulted in diminished DNA-PK activity and X-ray hypersensitivity and that a KARP-1 antibody significantly neutralized DNA-PK activity in vitro. Finally, we present data which suggests that KARP-1 may be primate-specific. These observations have important repercussions for mammalian DNA double-strand break repair.

Original languageEnglish (US)
Pages (from-to)3172-3184
Number of pages13
JournalEMBO Journal
Volume16
Issue number11
DOIs
StatePublished - Jun 2 1997
Externally publishedYes

Fingerprint

DNA-Activated Protein Kinase
Leucine Zippers
Autoantigens
Proteins
Double-Stranded DNA Breaks
Leucine
DNA
Repair
Genes
Catalytic DNA
Rubiaceae
DNA Repair
Primates
Exons
Catalytic Domain
Hypersensitivity
Cells
X-Rays
Cell Line
X rays

Keywords

  • DNA repair
  • DNA-PK
  • Ku86
  • Leucine zipper

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

KARP-1 : A novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity. / Myung, Kyungjae; He, Dong Ming; Lee, Sang; Hendrickson, Eric A.

In: EMBO Journal, Vol. 16, No. 11, 02.06.1997, p. 3172-3184.

Research output: Contribution to journalArticle

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