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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
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; Fibroblasts; Animals; Humans; Mice; Infertility, Male; Chromosome Breakage; Genomic Instability; Carrier Proteins; Nuclear Proteins; Histones; Transcription Factors; Signal Transduction; Spermatogenesis; DNA Repair; Gene Expression Regulation, Developmental; Radiation, Ionizing; Radiation Tolerance; Male; 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.
RMID: 0020134962
DOI: 10.1371/journal.pgen.1003298
Grant ID:
Appears in Collections:Animal and Veterinary Sciences publications

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