Ku70/Ku80 and DNA-dependent protein kinase catalytic subunit modulate RAG-mediated cleavage: Implications for the enforcement of the 12/23 rule

Dennis J. Sawchuk, Jorge Mansilla-Soto, Claudio Alarcon, Netai C. Singha, Hanno Langen, Marco E. Bianchi, Susan P. Lees-Miller, Michel C. Nussenzweig, Patricia Cortes

Research output: Contribution to journalArticlepeer-review

Abstract

The 12/23 rule is a critical step for regulation of V(D)J recombination. To date, only the RAG proteins and high mobility group protein 1 or 2 have been implicated in 12/23 regulation. Through protein fractionation and biochemical experiments, we find that Ku70/Ku80 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) modulate RAG-mediated cleavage. Modulation of cleavage by Ku70/80 and DNA-PKcs results in preferential inhibition of 12/12 and 23/23 DNA cleavage, thus increasing 12/23 rule specificity. This observation indicates that DNA repair factors, Ku70/80 and DNA-PKcs, might be present upstream of the DNA cleavage events and not recruited downstream as is currently thought, assigning new nonrepair functions to the DNA-dependent protein kinase.

Original languageEnglish
Pages (from-to)29821-29831
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number28
DOIs
Publication statusPublished - Jul 9 2004

ASJC Scopus subject areas

  • Biochemistry

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