Preprint Review Version 1 This version is not peer-reviewed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)

How to cite: Castañeda-Zegarra, S.; Fernandez-Berrocal, M.; Tkachov, M.; 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 (doi: 10.20944/preprints202005.0277.v1). Castañeda-Zegarra, S.; Fernandez-Berrocal, M.; Tkachov, M.; 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 (doi: 10.20944/preprints202005.0277.v1).

Abstract

The non-homologous end joining (NHEJ) DNA repair pathway is the main mechanism to repair DNA double strand breaks (DSBs) throughout the whole cell cycle. During NHEJ, core Ku70 and Ku80 subunits form the Ku heterodimer; Ku binds DSBs and promotes the recruitment of accessory factors (e.g., DNA-PKcs, PAXX, Mri) and downstream core factors (XLF, Lig4 and XRCC4). DSBs are induced during the V(D)J recombination in developing B and T lymphocytes to increase the repertoire of B and T cell receptors. Furthermore, DSBs are generated during the class switch recombination (CSR) in mature B lymphocytes, providing distinct effector functions of antibody heavy chain constant regions. The NHEJ is required for both V(D)J recombination and CSR. During the last decades, new NHEJ proteins have been reported, increasing the complexity of the molecular pathway. Multiple in vivo mouse models were generated and characterized to identify specific functions of NHEJ factors in the adaptive immune system. Here, we are summarizing available mouse models lacking one or several NHEJ factors, with a particular focus on early B cell development.

Subject Areas

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

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