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DNA repair and antibody diversification: the 53BP1 paradigm

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Item Type:Review
Title:DNA repair and antibody diversification: the 53BP1 paradigm
Creators Name:Kabrani, E., Saha, T. and Di Virgilio, M.
Abstract:The DNA double-strand break (DSB) repair factor 53BP1 has long been implicated in V(D)J and class switch recombination (CSR) of mammalian lymphocyte receptors. However, the dissection of the underlying molecular activities is hampered by a paucity of studies [V(D)J] and plurality of phenotypes (CSR) associated with 53BP1 deficiency. Here, we revisit the currently accepted roles of 53BP1 in antibody diversification in view of the recent identification of its downstream effectors in DSB protection and latest advances in genome architecture. We propose that, in addition to end protection, 53BP1-mediated end-tethering stabilization is essential for CSR. Furthermore, we support a pre-DSB role during V(D)J recombination. Our perspective underscores the importance of evaluating repair of DSBs in relation to their dynamic architectural contexts.
Keywords:Antibodies, Double-Stranded DNA Breaks, DNA Repair, Immunoglobulin Class Switching, Lymphocytes, Animals, Mammals
Source:Trends in Immunology
ISSN:1471-4906
Publisher:Elsevier
Volume:44
Number:10
Page Range:782-791
Date:October 2023
Official Publication:https://doi.org/10.1016/j.it.2023.08.004
PubMed:View item in PubMed

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