Working Paper Review Version 2 This version is not peer-reviewed

Genetic Interaction Between the Non-homologous End Joining Factors during B and T Lymphocyte Development: In Vivo Mouse Models

Version 1 : Received: 15 May 2020 / Approved: 16 May 2020 / Online: 16 May 2020 (18:36:09 CEST)
Version 2 : Received: 11 June 2020 / Approved: 12 June 2020 / Online: 12 June 2020 (07:53:17 CEST)

How to cite: Castañeda-Zegarra, S.; Fernandez-Berrocal, M.; Tkachov, M.; Yao, R.; Upfold, N.L.E.; Oksenych, V. Genetic Interaction Between the Non-homologous End Joining Factors during B and T Lymphocyte Development: In Vivo Mouse Models. Preprints 2020, 2020050277 Castañeda-Zegarra, S.; Fernandez-Berrocal, M.; Tkachov, M.; Yao, R.; Upfold, N.L.E.; Oksenych, V. Genetic Interaction Between the Non-homologous End Joining Factors during B and T Lymphocyte Development: In Vivo Mouse Models. Preprints 2020, 2020050277

Abstract

Non-homologous end joining (NHEJ) is the main DNA repair mechanism for the repair of double strand breaks (DSBs) throughout the course of the cell cycle. DSBs are generated in developing B and T lymphocytes during V(D)J recombination to increase the repertoire of B and T cell receptors. DSBs are also generated during the class switch recombination (CSR) process in mature B lymphocytes, providing distinct effector functions of antibody heavy chain constant regions. Thus, NHEJ is important for both V(D)J recombination and CSR. NHEJ comprises core Ku70 and Ku80 subunits that form the Ku heterodimer, which binds DSBs and promotes the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, PAXX, Mri) and downstream core factors (XLF, Lig4 and XRCC4). In recent decades, new NHEJ proteins have been reported, increasing complexity of this molecular pathway. Numerous in vivo mouse models have been generated and characterized to identify the interplay of NHEJ factors and their role in development of adaptive immune system. This review summarizes the currently available mouse models lacking one or several NHEJ factors, with a particular focus on early B cell development. We also underline genetic interactions and redundancy in the NHEJ pathway in mice.

Subject Areas

B cell; V(D)J recombination; mouse model; NHEJ; DNA repair

Comments (1)

Comment 1
Received: 12 June 2020
Commenter: Valentyn Oksenych
Commenter's Conflict of Interests: Author
Comment: We have replaced one Figure (former Figure 1 is removed, new Figure 2 is added), updated the text and references to make it more precise; English grammar was corrected
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