Classical and alternative end-joining pathways for repair of lymphocyte-specific and general DNA double-strand breaks

Adv Immunol. 2012;116:1-49. doi: 10.1016/B978-0-12-394300-2.00001-6.

Abstract

Classical nonhomologous end joining (C-NHEJ) is one of the two major known pathways for the repair of DNA double-strand breaks (DSBs) in mammalian cells. Our understanding of C-NHEJ has been derived, in significant part, through studies of programmed physiologic DNA DSBs formed during V(D)J recombination in the developing immune system. Studies of immunoglobulin heavy-chain (IgH) class-switch recombination (CSR) also have revealed that there is an "alternative" end-joining process (A-EJ) that can function, relatively robustly, in the repair of DSBs in activated mature B lymphocytes. This A-EJ process has also been implicated in the formation of oncogenic translocations found in lymphoid tumors. In this review, we discuss our current understanding of C-NHEJ and A-EJ in the context of V(D)J recombination, CSR, and the formation of chromosomal translocations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA Breaks, Double-Stranded*
  • DNA End-Joining Repair*
  • DNA Repair*
  • Humans
  • Immunoglobulin Class Switching
  • Lymphocytes / metabolism*
  • V(D)J Recombination