Queensland Institute of Medical Research, Herston, Australia.
PLoS Genet. 2013;9(2):e1003298. doi: 10.1371/journal.pgen.1003298. Epub 2013 Feb 7.
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.
单链 DNA 结合蛋白（SSBs）调节多种 DNA 代谢过程，包括复制、转录和修复。我们最近发现 SSB1 是一种新的蛋白，它对于 ATM 信号的起始和同源重组介导的 DNA 双链断裂修复至关重要。在此，我们报道 Ssb1(-/-) 胚胎由于严重的胸廓畸形和肺泡发育受损，以及额外的骨骼缺陷，出生时即死于呼吸衰竭。出乎意料的是，Ssb1(-/-) 成纤维细胞在受到电离辐射（IR）时，其 Atm 信号或 γ-H2ax 焦点动力学并没有缺陷，并且 B 细胞特异性敲除 Ssb1 也不会影响体外的类别转换重组。然而，在成年小鼠中条件性敲除 Ssb1 会导致广泛的肿瘤谱增加癌症易感性、睾丸退化导致的雄性生育力受损、以及体内辐射敏感性和 IR 诱导的染色体断裂增加。总之，这些结果表明 Ssb1 在体内胚胎发生、精子发生和基因组稳定性中发挥着重要作用。
