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KARP‐1: a novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA‐dependent protein kinase activity
Author(s) -
Myung Kyungjae,
He Dong Ming,
Lee Sang Eun,
Hendrickson Eric A.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.11.3172
Subject(s) - biology , leucine zipper , basic helix loop helix leucine zipper transcription factors , protein kinase a , bzip domain , genetics , locus (genetics) , microbiology and biotechnology , kinase , transcription factor , dna binding protein , gene
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 ( K u86 A utoantigen R elated P rotein‐ 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.