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Essential Developmental, Genomic Stability, and Tumour Suppressor Functions of the Mouse Orthologue of hSSB1/NABP2

Single-stranded DNA binding proteins (SSBs) regulate multiple DNA transactions, including replication, transcription, and repair. We recently identified SSB1 as a novel protein critical for the initiation of ATM signaling and DNA double-strand break repair by homologous recombination. Here we report...

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Autores principales: Shi, Wei, Bain, Amanda L., Schwer, Bjoern, Al-Ejeh, Fares, Smith, Corey, Wong, Lee, Chai, Hua, Miranda, Mariska S., Ho, Uda, Kawaguchi, Makoto, Miura, Yutaka, Finnie, John W., Wall, Meaghan, Heierhorst, Jörg, Wicking, Carol, Spring, Kevin J., Alt, Frederick W., Khanna, Kum Kum
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567186/
https://www.ncbi.nlm.nih.gov/pubmed/23408915
http://dx.doi.org/10.1371/journal.pgen.1003298
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author Shi, Wei
Bain, Amanda L.
Schwer, Bjoern
Al-Ejeh, Fares
Smith, Corey
Wong, Lee
Chai, Hua
Miranda, Mariska S.
Ho, Uda
Kawaguchi, Makoto
Miura, Yutaka
Finnie, John W.
Wall, Meaghan
Heierhorst, Jörg
Wicking, Carol
Spring, Kevin J.
Alt, Frederick W.
Khanna, Kum Kum
author_facet Shi, Wei
Bain, Amanda L.
Schwer, Bjoern
Al-Ejeh, Fares
Smith, Corey
Wong, Lee
Chai, Hua
Miranda, Mariska S.
Ho, Uda
Kawaguchi, Makoto
Miura, Yutaka
Finnie, John W.
Wall, Meaghan
Heierhorst, Jörg
Wicking, Carol
Spring, Kevin J.
Alt, Frederick W.
Khanna, Kum Kum
author_sort Shi, Wei
collection PubMed
description Single-stranded DNA binding proteins (SSBs) regulate multiple DNA transactions, including replication, transcription, and repair. We recently identified SSB1 as a novel protein critical for the initiation of ATM signaling and DNA double-strand break repair by homologous recombination. Here we report that germline Ssb1(−/−) embryos die at birth from respiratory failure due to severe rib cage malformation and impaired alveolar development, coupled with additional skeletal defects. Unexpectedly, Ssb1 (−/−) fibroblasts did not exhibit defects in Atm signaling or γ-H2ax focus kinetics in response to ionizing radiation (IR), and B-cell specific deletion of Ssb1 did not affect class-switch recombination in vitro. However, conditional deletion of Ssb1 in adult mice led to increased cancer susceptibility with broad tumour spectrum, impaired male fertility with testicular degeneration, and increased radiosensitivity and IR–induced chromosome breaks in vivo. Collectively, these results demonstrate essential roles of Ssb1 in embryogenesis, spermatogenesis, and genome stability in vivo.
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spelling pubmed-35671862013-02-13 Essential Developmental, Genomic Stability, and Tumour Suppressor Functions of the Mouse Orthologue of hSSB1/NABP2 Shi, Wei Bain, Amanda L. Schwer, Bjoern Al-Ejeh, Fares Smith, Corey Wong, Lee Chai, Hua Miranda, Mariska S. Ho, Uda Kawaguchi, Makoto Miura, Yutaka Finnie, John W. Wall, Meaghan Heierhorst, Jörg Wicking, Carol Spring, Kevin J. Alt, Frederick W. Khanna, Kum Kum PLoS Genet Research Article Single-stranded DNA binding proteins (SSBs) regulate multiple DNA transactions, including replication, transcription, and repair. We recently identified SSB1 as a novel protein critical for the initiation of ATM signaling and DNA double-strand break repair by homologous recombination. Here we report that germline Ssb1(−/−) embryos die at birth from respiratory failure due to severe rib cage malformation and impaired alveolar development, coupled with additional skeletal defects. Unexpectedly, Ssb1 (−/−) fibroblasts did not exhibit defects in Atm signaling or γ-H2ax focus kinetics in response to ionizing radiation (IR), and B-cell specific deletion of Ssb1 did not affect class-switch recombination in vitro. However, conditional deletion of Ssb1 in adult mice led to increased cancer susceptibility with broad tumour spectrum, impaired male fertility with testicular degeneration, and increased radiosensitivity and IR–induced chromosome breaks in vivo. Collectively, these results demonstrate essential roles of Ssb1 in embryogenesis, spermatogenesis, and genome stability in vivo. Public Library of Science 2013-02-07 /pmc/articles/PMC3567186/ /pubmed/23408915 http://dx.doi.org/10.1371/journal.pgen.1003298 Text en © 2013 Shi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Shi, Wei
Bain, Amanda L.
Schwer, Bjoern
Al-Ejeh, Fares
Smith, Corey
Wong, Lee
Chai, Hua
Miranda, Mariska S.
Ho, Uda
Kawaguchi, Makoto
Miura, Yutaka
Finnie, John W.
Wall, Meaghan
Heierhorst, Jörg
Wicking, Carol
Spring, Kevin J.
Alt, Frederick W.
Khanna, Kum Kum
Essential Developmental, Genomic Stability, and Tumour Suppressor Functions of the Mouse Orthologue of hSSB1/NABP2
title Essential Developmental, Genomic Stability, and Tumour Suppressor Functions of the Mouse Orthologue of hSSB1/NABP2
title_full Essential Developmental, Genomic Stability, and Tumour Suppressor Functions of the Mouse Orthologue of hSSB1/NABP2
title_fullStr Essential Developmental, Genomic Stability, and Tumour Suppressor Functions of the Mouse Orthologue of hSSB1/NABP2
title_full_unstemmed Essential Developmental, Genomic Stability, and Tumour Suppressor Functions of the Mouse Orthologue of hSSB1/NABP2
title_short Essential Developmental, Genomic Stability, and Tumour Suppressor Functions of the Mouse Orthologue of hSSB1/NABP2
title_sort essential developmental, genomic stability, and tumour suppressor functions of the mouse orthologue of hssb1/nabp2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567186/
https://www.ncbi.nlm.nih.gov/pubmed/23408915
http://dx.doi.org/10.1371/journal.pgen.1003298
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