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Recent Insights into the Formation of RAG-Induced Chromosomal Translocations

  • Chapter
V(D)J Recombination

Part of the book series: Advances in Experimental Medicine and Biology ((volume 650))

Abstract

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.

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  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 Medicine, New York University School of Medicine, New York, New York, 10016, USA

    Vicky L. Brandt & David B. Roth

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  1. Vicky L. Brandt
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  1. Centre d’Immunologie de Marseille-Luminy, Université d’Aix Marseille, Marseille, France

    Pierre Ferrier MD, PhD

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Brandt, V.L., Roth, D.B. (2009). Recent Insights into the Formation of RAG-Induced Chromosomal Translocations. In: Ferrier, P. (eds) V(D)J Recombination. Advances in Experimental Medicine and Biology, vol 650. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0296-2_3

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