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53BP1 supports immunoglobulin class switch recombination independently of its DNA double-strand break end protection function

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Item Type:Article
Title:53BP1 supports immunoglobulin class switch recombination independently of its DNA double-strand break end protection function
Creators Name:Sundaravinayagam, D. and Rahjouei, A. and Andreani, M. and Tupiņa, D. and Balasubramanian, S. and Saha, T. and Delgado-Benito, V. and Coralluzzo, V. and Daumke, O. and Di Virgilio, M.
Abstract:Class switch recombination (CSR) is a DNA recombination reaction that diversifies the effector functions of antibodies. CSR occurs via the formation and non-homologous end joining (NHEJ) repair of programmed DNA double-strand breaks (DSBs) at the immunoglobulin heavy chain locus. The DNA repair factors 53BP1 and Rif1 promote NHEJ and CSR by protecting DSBs against resection. However, to what extent repression of DNA end resection contributes to CSR is unknown. Here, we show that B lymphocytes devoid of 53BP1-Rif1-dependent DSB end protection activity undergo robust CSR. Inactivation of specific sets of phospho-sites within 53BP1 N-terminal SQ/TQ motifs abrogates Rif1 recruitment and inhibition of resection but only mildly reduces CSR. Furthermore, mutations within 53BP1 oligomerization domain abolish CSR without substantially affecting DNA end processing. Thus, inhibition of DNA end resection does not correlate with CSR efficiency, indicating that regulation of DSB processing is not a key determinant step in CSR.
Keywords:Class Switch Recombination, NHEJ, DNA End Resection, 53BP1, Rif1, Animals, Mice
Source:Cell Reports
ISSN:2211-1247
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:28
Number:6
Page Range:1389-1399
Date:6 August 2019
Official Publication:https://doi.org/10.1016/j.celrep.2019.06.035
PubMed:View item in PubMed

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