Restrictions limiting the generation of DNA double strand breaks during chromosomal V(D)J recombination

Robert E. Tillman, Andrea L. Wooley, Maureen M. Hughes, Tara D. Wehrly, Wojciech Swat, Barry P. Sleckman

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Antigen receptor loci are composed of numerous variable (V), diversity (D), and joining (J) gene segments, each flanked by recombination signal sequences (RSSs). The V(D)J recombination reaction proceeds through RSS recognition and DNA cleavage steps making it possible for multiple DNA double strand breaks (DSBs) to be introduced at a single locus. Here we use ligation-mediated PCR to analyze DNA cleavage intermediates in thymocytes from mice with targeted RSS mutations at the endogenous TCRβ locus. We show that DNA cleavage does not occur at individual RSSs but rather must be coordinated between RSS pairs flanking gene segments that ultimately form coding joins. Coordination of the DNA cleavage step occurs over great distances in the chromosome and favors intra- over interchromosomal recombination. Furthermore, through several restrictions imposed on the generation of both nonpaired and paired DNA DSBs, this requirement promotes antigen receptor gene integrity and genomic stability in developing lymphocytes undergoing V(D)J recombination.

Original languageEnglish
Pages (from-to)309-316
Number of pages8
JournalJournal of Experimental Medicine
Issue number3
StatePublished - Feb 4 2002


  • Antigen receptor
  • DNA cleavage
  • DNA repair
  • Lymphocyte
  • RAG


Dive into the research topics of 'Restrictions limiting the generation of DNA double strand breaks during chromosomal V(D)J recombination'. Together they form a unique fingerprint.

Cite this