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

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    Author(s)
    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, Jorg
    Wicking, Carol
    Spring, Kevin J
    Alt, Frederick W
    Khanna, Kum Kum
    Griffith University Author(s)
    Spring, Kevin
    Khanna, Kum K.
    Bain, Amanda L.
    Year published
    2013
    Metadata
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    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 ...
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    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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    Journal Title
    PLoS Genetics
    Volume
    9
    Issue
    2
    DOI
    https://doi.org/10.1371/journal.pgen.1003298
    Copyright Statement
    © 2013 Shi et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)
    Subject
    Human Geography not elsewhere classified
    Genetics
    Publication URI
    http://hdl.handle.net/10072/60378
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