title: Essential developmental, genomic stability, and tumour suppressor functions of the mouse orthologue of hSSB1/NABP2.
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.
authors: Queensland Institute of Medical Research, Herston, Australia.
authors: Wei
authors: W
authors: Shi
authors: Amanda L
authors: AL
authors: Bain
authors: Bjoern
authors: B
authors: Schwer
authors: Fares
authors: F
authors: Al-Ejeh
authors: Corey
authors: C
authors: Smith
authors: Lee
authors: L
authors: Wong
authors: Hua
authors: H
authors: Chai
authors: Mariska S
authors: MS
authors: Miranda
authors: Uda
authors: U
authors: Ho
authors: Makoto
authors: M
authors: Kawaguchi
authors: Yutaka
authors: Y
authors: Miura
authors: John W
authors: JW
authors: Finnie
authors: Meaghan
authors: M
authors: Wall
authors: Jörg
authors: J
authors: Heierhorst
authors: Carol
authors: C
authors: Wicking
authors: Kevin J
authors: KJ
authors: Spring
authors: Frederick W
authors: FW
authors: Alt
authors: Kum Kum
authors: KK
authors: Khanna
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D019457:Chromosome Breakage / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D042822:Genomic Instability / Q000235:genetics; D006657:Histones / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000235:genetics; D013091:Spermatogenesis; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
chemical_list: C554480:ATMIN protein, mouse; D002352:Carrier Proteins; D006657:Histones; D009687:Nuclear Proteins; C515022:SSB-1 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; C475961:gamma-H2AX protein, mouse