The Response to and Repair of RAG-Mediated DNA Double-Strand Breaks
Year: 2012
Type: review
Abstract: Developing lymphocytes must assemble antigen receptor genes encoding the B cell and T cell receptors. This process is executed by the V(D)J recombination reaction, which can be divided into DNA cleavage and DNA joining steps. The former is carried out by a lymphocyte-specific RAG endonuclease, which mediates DNA cleavage at two recombining gene segments and their flanking RAG recognition sequences. RAG cleavage generates four broken DNA ends that are repaired by nonhomologous end joining forming coding and signal joints. On rare occasions, these DNA ends may join aberrantly forming chromosomal lesions such as translocations, deletions and inversions that have the potential to cause cellular transformation and lymphoid tumors. We discuss the activation of DNA damage responses by RAG-induced DSBs focusing on the component pathways that promote their normal repair and guard against their aberrant resolution. Moreover, we discuss how this DNA damage response impacts processes important for lymphocyte development.
Source: Annual Review of Immunology
Authors: Beth A. Helmink, Barry P. Sleckman
Institution: Washington University in St. Louis
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2168265716