Smith, AL, Scott, JNF and Boyes, J orcid.org/0000-0002-8705-9827 (2019) The ESC: The Dangerous by-product of V(D)J Recombination. Frontiers in Immunology, 10. 1572. ISSN 1664-3224
Abstract
V(D)J recombination generates antigen receptor diversity by mixing and matching individual variable (V), diversity (D), and joining (J) gene segments. An obligate by-product of many of these reactions is the excised signal circle (ESC), generated by excision of the DNA from between the gene segments. Initially, the ESC was believed to be inert and formed to protect the genome from reactive broken DNA ends but more recent work suggests that the ESC poses a substantial threat to genome stability. Crucially, the recombinase re-binds to the ESC, which can result in it being re-integrated back into the genome, to cause potentially oncogenic insertion events. In addition, very recently, the ESC/recombinase complex was found to catalyze breaks at recombination signal sequences (RSSs) throughout the genome, via a “cut-and-run” mechanism. Remarkably, the ESC/recombinase complex triggers these breaks at key leukemia driver genes, implying that this reaction could be a significant cause of lymphocyte genome instability. Here, we explore these alternate pathways and discuss their relative dangers to lymphocyte genome stability.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Smith, Scott and Boyes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/ |
Keywords: | V(D)J recombination; RAG proteins; genome instability; Leukemia; Double Strand Breaks |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Molecular & Cellular Biology (Leeds) |
Funding Information: | Funder Grant number NC3Rs NC/K001639/1 Bloodwise 15042 |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Jun 2019 15:22 |
Last Modified: | 25 Jun 2023 21:52 |
Status: | Published |
Publisher: | Frontiers Media |
Identification Number: | 10.3389/fimmu.2019.01572 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:147749 |