NHEJ and Other Repair Factors in V(D)J Recombination

Abstract

V(D)J recombination requires the formation and resolution of programmed DNA double-strand breaks (DSBs) to effect the gene rearrangements necessary for immunoglobulin and T cell receptor formation. Improper repair of DNA DSBs can lead to deleterious consequences for the cell, including loss of genetic information, cell death, and formation of chromosomal translocations. The classical nonhomologous end-joining (C-NHEJ) pathway is a major DNA DSB repair pathway that maintains cellular genomic integrity in response to DNA DSBs. The V(D)J recombination reaction absolutely requires C-NHEJ for DSB repair. In addition to this requirement, C-NHEJ also contributes to the diversity of antigen receptor molecules through the processing of DNA DSBs prior to their repair. In this article, we discuss the C-NHEJ pathway in the context of the V(D)J recombination reaction. We outline the major phases of C-NHEJ, how C-NHEJ handles the different species of DNA DSBs generated during V(D)J recombination, and the protein players known to be involved in C-NHEJ. The joining phase of V(D)J recombination has provided a rich context for understanding not only how antigen receptors form but also how DNA DSB repair occurs more generally in cells.