Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed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

Sergio Castañeda-Zegarra
ORCID logo ,
Marion Fernandez-Berrocal
,
Max Tkachov
,
Nikki Lyn Esnardo Upfold
ORCID logo ,
Valentyn Oksenych
* ORCID logo
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)

A peer-reviewed article of this Preprint also exists.

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. Scandinavian Journal of Immunology 2020, 92, doi:10.1111/sji.12936. 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. Scandinavian Journal of Immunology 2020, 92, doi:10.1111/sji.12936.

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.

Keywords

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

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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