FIGURE 1.

V(D)J recombination and NHEJ Basics: Generating antigen receptor diversity. (A) V(D)J recombination at the immunoglobulin heavy chain locus (depicted as an example) consists in a sequential 2-step rearrangement of V, D and J segments. This combinatorial process generates the diversity of antigen receptors. (B) After RAG cleavage, the NHEJ repair pathway is initiated by binding of the Ku70/80 heterodimer (Ku) to DNA ends. Ku together with DNA-PKcs form the DNA-PK holoenzyme. RAG DNA ends are then processed by the endonuclease Artemis and polymerases (e.g., Pol µ), specifically the terminal deoxynucleotidyl transferase (TdT), resulting in increased junctional diversity (in gray). This additional diversity is generated, prior to joining, in two forms: 1) P- palindromic sequences, produced through the endonuclease action of Artemis at RAG-induced hairpin-sealed ends and 2) N-nucleotide sequences, the addition of non-templated nucleotides by TdT. Finally, the ligation complex composed of Ligase IV, XRCC4 and XLF joins the processed ends. Joining of DNA ends via NHEJ further participates to generating indels, moreover favoring junctional diversity. NHEJ: non-homologous end-joining, indels: insertions or deletions.