Modulation of terminal deoxynucleotidyltransferase activity by the DNA- dependent protein kinase

Scott Mickelsen, Carolyn Snyder, Kelly Trujillo, Molly Bogue, David B. Roth, Katheryn Meek

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42 Scopus citations

Abstract

Rare Ig and TCR coding joints can be isolated from mice that have a targeted deletion in the gene encoding the 86-kDa subunit of the Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase (DNA- PK). However in the coding joints isolated from Ku86(-/-) animals, there is an extreme paucity of N regions (the random nucleotides added during V(D)J recombination by the enzyme TdT). This finding is consistent with a decreased frequency of coding joints containing N regions isolated from C.B-17 SCID mice that express a truncated form of the catalytic subunit of the DNA-PK (DNA-PK(CS)). This finding suggests an unexpected role for DNA-PK in addition of N nucleotides to coding ends during V(D)J recombination. In this report, we establish that TdT forms a stable complex with DNA-PK. Furthermore, we show that DNA-PK modulates TdT activity in vitro by limiting both the length and composition of nucleotide additions.

Original languageEnglish (US)
Pages (from-to)834-843
Number of pages10
JournalJournal of Immunology
Volume163
Issue number2
Publication statusPublished - Jul 15 1999

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Mickelsen, S., Snyder, C., Trujillo, K., Bogue, M., Roth, D. B., & Meek, K. (1999). Modulation of terminal deoxynucleotidyltransferase activity by the DNA- dependent protein kinase. Journal of Immunology, 163(2), 834-843.