Recent Insights into the Formation of RAG-Induced Chromosomal Translocations

  • Vicky L. Brandt
  • David B. RothEmail author
Part of the Advances in Experimental Medicine and Biology book series (volume 650)


Chromosomal translocations are found in many types of tumors, where they may be either a cause or a result of malignant transformation. In lymphoid neoplasms, however, it is clear that pathogenesis is initiated by any of a number of recurrent DNA rearrangements. These particular translocations typically place an oncogene under the regulatory control of an Ig or TCR gene promoter, dysregulating cell growth, differentiation, or apoptosis. Given that physiological DNA rearrangements (V(D)J and class switch recombination) are integral to lymphocyte development, it is critical to understand how genomic stability is maintained during these processes. Recent advances in our understanding of DNA damage signaling and repair have provided clues to the kinds of mechanisms that lead to V(D)J-mediated translocations. In turn, investigations into the regulation of V(D)J joining have illuminated a formerly obscure pathway of DNA repair known as alternative NHEJ, which is error-prone and frequently involved in translocations. In this chapter we consider recent advances in our understanding of the functions of the RAG proteins, RAG interactions with DNA repair pathways, damage signaling and chromosome biology, all of which shed light on how mistakes at different stages of V(D)J recombination might lead to leukemias and lymphomas.


Chromosomal Translocation Lymphoid Neoplasm NijmegenBreakage Syndrome Recombination Signal Sequence Antigen Receptor Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  1. 1.Department of Pathology and Program in Molecular Pathogenesis The Helen L. and Martin S. Kimmel Center for Biology and Medicine Skirball Institute for Biomolecular MedicineNew York University School of MedicineNew YorkUSA

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