Alternative end-joining in BCR gene rearrangements and translocations

Acta Biochim Biophys Sin (Shanghai). 2022 May 25;54(6):782-795. doi: 10.3724/abbs.2022051.

Abstract

Programmed DNA double-strand breaks (DSBs) occur during antigen receptor gene recombination, namely V(D)J recombination in developing B lymphocytes and class switch recombination (CSR) in mature B cells. Repair of these DSBs by classical end-joining (c-NHEJ) enables the generation of diverse BCR repertoires for efficient humoral immunity. Deletion of or mutation in c-NHEJ genes in mice and humans confer various degrees of primary immune deficiency and predisposition to lymphoid malignancies that often harbor oncogenic chromosomal translocations. In the absence of c-NHEJ, alternative end-joining (A-EJ) catalyzes robust CSR and to a much lesser extent, V(D)J recombination, but the mechanisms of A-EJ are only poorly defined. In this review, we introduce recent advances in the understanding of A-EJ in the context of V(D)J recombination and CSR with emphases on DSB end processing, DNA polymerases and ligases, and discuss the implications of A-EJ to lymphoid development and chromosomal translocations.

Keywords: DSB end resection; V(D)J recombination; alternative end-joining; chromosomal translocation; classical nonhomologous end-joining; endonuclease.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA
  • DNA End-Joining Repair* / genetics
  • Humans
  • Immunoglobulin Class Switching / genetics
  • Ligases / genetics
  • Mice
  • Receptors, Antigen, B-Cell* / genetics
  • Translocation, Genetic*

Substances

  • Receptors, Antigen, B-Cell
  • DNA
  • Ligases