耐低氧盲鼹鼠对 DNA 损伤的抵抗和增强的 DNA 修复能力。
Resistance to DNA damage and enhanced DNA repair capacity in the hypoxia-tolerant blind mole rat .
机构信息
The Institute of Evolution and Department of Evolutionary and Environmental Biology, University of Haifa, Haifa 3498838, Israel.
The Institute of Evolution and Department of Evolutionary and Environmental Biology, University of Haifa, Haifa 3498838, Israel
出版信息
J Exp Biol. 2018 Apr 20;221(Pt 8):jeb174540. doi: 10.1242/jeb.174540.
Blind mole rats of the genus are the only mammalian species to date for which spontaneous cancer has never been reported and resistance to carcinogen-induced cancers has been demonstrated. However, the underlying mechanisms are still poorly understood. The fact that spp. are also hypoxia-tolerant and long-lived species implies the presence of molecular adaptations to prevent genomic instability, which underlies both cancer and aging. We previously demonstrated the upregulation of transcripts related to DNA replication and repair pathways in Yet, to date, no direct experimental evidence for improved genomic maintenance has been demonstrated for this genus. Here, we show that compared with skin fibroblasts of the above-ground rat, skin fibroblasts in culture resist several types of genotoxic insult, accumulate fewer genotoxic lesions and exhibit an enhanced DNA repair capacity. Our results strongly support that this species has evolved efficient mechanisms to maintain DNA integrity as an adaptation to the stressful conditions in the subterranean habitat.
盲鼹鼠属的鼹鼠是目前为止唯一一种尚未报道自发性癌症且对致癌物诱导的癌症具有抗性的哺乳动物物种。然而,其潜在机制仍知之甚少。事实上,该属的物种还具有耐缺氧和长寿的特性,这意味着存在分子适应机制来防止基因组不稳定性,而基因组不稳定性是癌症和衰老的基础。我们之前已经证明了与 DNA 复制和修复途径相关的转录本在盲鼹鼠中上调。然而,迄今为止,尚未证明该属具有改善基因组维持的直接实验证据。在这里,我们表明与地面上的大鼠的皮肤成纤维细胞相比,培养中的盲鼹鼠皮肤成纤维细胞能抵抗多种类型的遗传毒性损伤,积累更少的遗传毒性损伤,并表现出增强的 DNA 修复能力。我们的研究结果有力地支持了这样一种观点,即这种物种已经进化出有效的机制来维持 DNA 完整性,作为对地下栖息地应激条件的适应。