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Type: Journal article
Title: Essential developmental, genomic stability, and tumour suppressor functions of the mouse orthologue of hSSB1/NABP2
Author: Shi, W.
Bain, A.
Schwer, B.
Al-ejeh, F.
Smith, C.
Wong, L.
Chai, H.
Miranda, M.
Ho, U.
Kawaguchi, M.
Miura, Y.
Finnie, J.
Wall, M.
Heierhorst, J.
Wicking, C.
Spring, K.
Alt, F.
Khanna, K.
Citation: PLoS Genetics, 2013; 9(2):1-19
Publisher: Public Library of Science
Issue Date: 2013
ISSN: 1553-7390
Editor: McKinnon, P.
Statement of
Wei Shi, Amanda L. Bain, Bjoern Schwer, Fares Al-Ejeh, Corey Smith, Lee Wong, Hua Chai, Mariska S. Miranda, Uda Ho, Makoto Kawaguchi, Yutaka Miura, John W. Finnie, Meaghan Wall, Jörg Heierhorst, Carol Wicking, Kevin J. Spring, Frederick W. Alt, Kum Kum Khanna
Abstract: 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.
Keywords: B-Lymphocytes
Infertility, Male
Chromosome Breakage
Genomic Instability
Carrier Proteins
Nuclear Proteins
Transcription Factors
Signal Transduction
DNA Repair
Gene Expression Regulation, Developmental
Radiation, Ionizing
Radiation Tolerance
Suppressor of Cytokine Signaling Proteins
DNA Breaks, Double-Stranded
Homologous Recombination
Rights: © 2013 Shi et al. 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 credited.
DOI: 10.1371/journal.pgen.1003298
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Appears in Collections:Animal and Veterinary Sciences publications
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