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

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

Research output: Contribution to journalArticle

42 Citations (Scopus)

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
StatePublished - Jul 15 1999

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DNA-Activated Protein Kinase
DNA Nucleotidylexotransferase
V(D)J Recombination
Nucleotides
Joints
DNA
Catalytic DNA
SCID Mice
Gene Deletion
Catalytic Domain
Enzymes

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.

Modulation of terminal deoxynucleotidyltransferase activity by the DNA- dependent protein kinase. / Mickelsen, Scott; Snyder, Carolyn; Trujillo, Kelly; Bogue, Molly; Roth, David B.; Meek, Katheryn.

In: Journal of Immunology, Vol. 163, No. 2, 15.07.1999, p. 834-843.

Research output: Contribution to journalArticle

Mickelsen, S, Snyder, C, Trujillo, K, Bogue, M, Roth, DB & Meek, K 1999, 'Modulation of terminal deoxynucleotidyltransferase activity by the DNA- dependent protein kinase', Journal of Immunology, vol. 163, no. 2, pp. 834-843.
Mickelsen S, Snyder C, Trujillo K, Bogue M, Roth DB, Meek K. Modulation of terminal deoxynucleotidyltransferase activity by the DNA- dependent protein kinase. Journal of Immunology. 1999 Jul 15;163(2):834-843.
Mickelsen, Scott ; Snyder, Carolyn ; Trujillo, Kelly ; Bogue, Molly ; Roth, David B. ; Meek, Katheryn. / Modulation of terminal deoxynucleotidyltransferase activity by the DNA- dependent protein kinase. In: Journal of Immunology. 1999 ; Vol. 163, No. 2. pp. 834-843.
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