Unique and redundant functions of ATM and DNA-PKcs during V(D)J recombination

Eric J. Gapud, Barry P. Sleckman

Research output: Contribution to journalReview articlepeer-review

Abstract

Lymphocyte antigen receptor genes are assembled through the process of V(D)J recombination during which pairwise DNA cleavage of gene segments results in the formation of four DNA ends that are resolved into a coding joint and a signal joint. The joining of these DNA ends occurs in G1-phase lymphocytes and is mediated by the non-homologous end-joining (NHEJ) pathway of DNA double strand break (DSB) repair. The ataxia telangiectasia mutated (ATM) and the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), two related kinases, both function in the repair of DNA breaks generated during antigen receptor gene assembly. Although these proteins have unique functions during coding joint formation, their activities in signal joint formation, if any, have been less clear. However, two recent studies demonstrated that ATM and DNA-PKcs have overlapping activities important for signal joint formation. Here we discuss the unique and shared activities of the ATM and DNA-PKcs kinases during V(D)J recombination, a process that is essential for lymphocyte development and the diversification of antigen receptors.

Original languageEnglish (US)
Pages (from-to)1928-1935
Number of pages8
JournalCell Cycle
Volume10
Issue number12
DOIs
StatePublished - Jun 15 2011

Keywords

  • ATM
  • DNA repair
  • DNA-PKcs
  • Lymphocyte
  • RAG
  • V(D)J recombination

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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