PDF(Pubmed)
Abstract：
Tardigrades are microscopic animals renowned for their ability to withstand extreme conditions, including high doses of ionizing radiation (IR). To better understand their radio-resistance, we first characterized induction and repair of DNA double- and single-strand breaks after exposure to IR in the model species Hypsibius exemplaris. Importantly, we found that the rate of single-strand breaks induced was roughly equivalent to that in human cells, suggesting that DNA repair plays a predominant role in tardigrades\' radio-resistance. To identify novel tardigrade-specific genes involved, we next conducted a comparative transcriptomics analysis across three different species. In all three species, many DNA repair genes were among the most strongly overexpressed genes alongside a novel tardigrade-specific gene, which we named Tardigrade DNA damage Response 1 (TDR1). We found that TDR1 protein interacts with DNA and forms aggregates at high concentration suggesting it may condensate DNA and preserve chromosome organization until DNA repair is accomplished. Remarkably, when expressed in human cells, TDR1 improved resistance to Bleomycin, a radiomimetic drug. Based on these findings, we propose that TDR1 is a novel tardigrade-specific gene conferring resistance to IR. Our study sheds light on mechanisms of DNA repair helping cope with high levels of DNA damage inflicted by IR.
摘要：
缓步动物是以其承受极端条件的能力而闻名的微小动物，包括高剂量的电离辐射（IR）。为了更好地了解他们的无线电抗性，我们首先在模型物种Hypsibius中描述了暴露于IR后DNA双链和单链断裂的诱导和修复。重要的是,我们发现诱导的单链断裂的速率大致相当于人类细胞的速率，这表明DNA修复在缓行放射性抵抗中起着主导作用。为了鉴定涉及的新型缓步特异性基因，接下来，我们对三个不同物种进行了比较转录组学分析。在所有三个物种中，许多DNA修复基因是最强烈的过度表达的基因之一，除了一个新的延迟特异性基因，我们将其命名为TardgradeDNA损伤反应1（TDR1）。我们发现TDR1蛋白与DNA相互作用，并在高浓度下形成聚集体，表明它可能会缩合DNA并保留染色体组织，直到完成DNA修复。值得注意的是,当在人类细胞中表达时，TDR1提高了对博来霉素的抗性，一种放射模拟药物.基于这些发现,我们认为TDR1是一种新的缓行特异性基因，赋予对IR的抗性。我们的研究揭示了有助于应对IR造成的高水平DNA损伤的DNA修复机制。
