Journal
ANNUAL REVIEW OF IMMUNOLOGY, VOL 30
Volume 30, Issue -, Pages 175-202Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-immunol-030409-101320
Keywords
antigen receptor genes; DNA damage responses; genomic stability; lymphocyte development; lymphoid tumors
Categories
Funding
- NCI NIH HHS [R01 CA136470, CA136470] Funding Source: Medline
- NIAID NIH HHS [R01 AI074953, AI47829, R01 AI047829, AI074953] Funding Source: Medline
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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 non-homologous 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.
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