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Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren

Classical non-homologous end joining (NHEJ) is a molecular pathway that detects, processes, and ligates DNA double-strand breaks (DSBs) throughout the cell cycle. Mutations in several NHEJ genes result in neurological abnormalities and immunodeficiency both in humans and mice. The NHEJ pathway is re...

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Autores principales: Castañeda-Zegarra, Sergio, Huse, Camilla, Røsand, Øystein, Sarno, Antonio, Xing, Mengtan, Gago-Fuentes, Raquel, Zhang, Qindong, Alirezaylavasani, Amin, Werner, Julia, Ji, Ping, Liabakk, Nina-Beate, Wang, Wei, Bjørås, Magnar, Oksenych, Valentyn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995585/
https://www.ncbi.nlm.nih.gov/pubmed/31795137
http://dx.doi.org/10.3390/biom9120798
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author Castañeda-Zegarra, Sergio
Huse, Camilla
Røsand, Øystein
Sarno, Antonio
Xing, Mengtan
Gago-Fuentes, Raquel
Zhang, Qindong
Alirezaylavasani, Amin
Werner, Julia
Ji, Ping
Liabakk, Nina-Beate
Wang, Wei
Bjørås, Magnar
Oksenych, Valentyn
author_facet Castañeda-Zegarra, Sergio
Huse, Camilla
Røsand, Øystein
Sarno, Antonio
Xing, Mengtan
Gago-Fuentes, Raquel
Zhang, Qindong
Alirezaylavasani, Amin
Werner, Julia
Ji, Ping
Liabakk, Nina-Beate
Wang, Wei
Bjørås, Magnar
Oksenych, Valentyn
author_sort Castañeda-Zegarra, Sergio
collection PubMed
description Classical non-homologous end joining (NHEJ) is a molecular pathway that detects, processes, and ligates DNA double-strand breaks (DSBs) throughout the cell cycle. Mutations in several NHEJ genes result in neurological abnormalities and immunodeficiency both in humans and mice. The NHEJ pathway is required for V(D)J recombination in developing B and T lymphocytes, and for class switch recombination in mature B cells. The Ku heterodimer formed by Ku70 and Ku80 recognizes DSBs and facilitates the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, Paxx and Mri/Cyren) and downstream core factor subunits X-ray repair cross-complementing group 4 (XRCC4), XRCC4-like factor (XLF), and DNA ligase 4 (Lig4). Accessory factors might be dispensable for the process, depending on the genetic background and DNA lesion type. To determine the physiological role of Mri in DNA repair and development, we introduced a frame-shift mutation in the Mri gene in mice. We then analyzed the development of Mri-deficient mice as well as wild type and immunodeficient controls. Mice lacking Mri possessed reduced levels of class switch recombination in B lymphocytes and slow proliferation of neuronal progenitors when compared to wild type littermates. Human cell lines lacking Mri were as sensitive to DSBs as the wild type controls. Overall, we concluded that Mri/Cyren is largely dispensable for DNA repair and mouse development.
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spelling pubmed-69955852020-02-13 Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren Castañeda-Zegarra, Sergio Huse, Camilla Røsand, Øystein Sarno, Antonio Xing, Mengtan Gago-Fuentes, Raquel Zhang, Qindong Alirezaylavasani, Amin Werner, Julia Ji, Ping Liabakk, Nina-Beate Wang, Wei Bjørås, Magnar Oksenych, Valentyn Biomolecules Article Classical non-homologous end joining (NHEJ) is a molecular pathway that detects, processes, and ligates DNA double-strand breaks (DSBs) throughout the cell cycle. Mutations in several NHEJ genes result in neurological abnormalities and immunodeficiency both in humans and mice. The NHEJ pathway is required for V(D)J recombination in developing B and T lymphocytes, and for class switch recombination in mature B cells. The Ku heterodimer formed by Ku70 and Ku80 recognizes DSBs and facilitates the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, Paxx and Mri/Cyren) and downstream core factor subunits X-ray repair cross-complementing group 4 (XRCC4), XRCC4-like factor (XLF), and DNA ligase 4 (Lig4). Accessory factors might be dispensable for the process, depending on the genetic background and DNA lesion type. To determine the physiological role of Mri in DNA repair and development, we introduced a frame-shift mutation in the Mri gene in mice. We then analyzed the development of Mri-deficient mice as well as wild type and immunodeficient controls. Mice lacking Mri possessed reduced levels of class switch recombination in B lymphocytes and slow proliferation of neuronal progenitors when compared to wild type littermates. Human cell lines lacking Mri were as sensitive to DSBs as the wild type controls. Overall, we concluded that Mri/Cyren is largely dispensable for DNA repair and mouse development. MDPI 2019-11-28 /pmc/articles/PMC6995585/ /pubmed/31795137 http://dx.doi.org/10.3390/biom9120798 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Castañeda-Zegarra, Sergio
Huse, Camilla
Røsand, Øystein
Sarno, Antonio
Xing, Mengtan
Gago-Fuentes, Raquel
Zhang, Qindong
Alirezaylavasani, Amin
Werner, Julia
Ji, Ping
Liabakk, Nina-Beate
Wang, Wei
Bjørås, Magnar
Oksenych, Valentyn
Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren
title Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren
title_full Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren
title_fullStr Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren
title_full_unstemmed Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren
title_short Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren
title_sort generation of a mouse model lacking the non-homologous end-joining factor mri/cyren
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995585/
https://www.ncbi.nlm.nih.gov/pubmed/31795137
http://dx.doi.org/10.3390/biom9120798
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