We have recently reported that cell-free DNA (cfDNA) fragments derived from dying cells that circulate in blood are biologically active molecules and can readily enter into healthy cells to activate DNA damage and apoptotic responses in the recipients. However, DNA is not conventionally known to spontaneously enter into cells or to have any intrinsic biological activity. We hypothesized that cellular entry and acquisition of biological properties are functions of the size of DNA. To test this hypothesis, we generated small DNA fragments by sonicating high molecular weight DNA (HMW DNA) to mimic circulating cfDNA. Sonication of HMW DNA isolated from cancerous and non-cancerous human cells, bacteria and plant generated fragments 300–3000 bp in size which are similar to that reported for circulating cfDNA. We show here that while HMW DNAs were incapable of entering into cells, sonicated DNA (sDNA) from different sources could do so indiscriminately without heed to species or kingdom boundaries. Thus, sDNA from human cells and those from bacteria and plant could enter into nuclei of mouse cells and sDNA from human, bacterial and plant sources could spontaneously enter into bacteria. The intracellular sDNA associated themselves with host cell chromosomes and integrated into their genomes. Furthermore, sDNA, but not HMW DNA, from all four sources could phosphorylate H2AX and activate the pro-inflammatory transcription factor NFκB in mouse cells, indicating that sDNAs had acquired biological activities. Our results show that small fragments of DNA from different sources can indiscriminately enter into other cells across species and kingdom boundaries to integrate into their genomes and activate biological processes. This raises the possibility that fragmented DNA that are generated following organismal cell-death may have evolutionary implications by acting as mobile genetic elements that are involved in horizontal gene transfer.

中文翻译：

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物理剪切使DNA具有生物活性，并具有跨物种和界界水平水平传播自身的能力。

我们最近报道，血液中循环的垂死细胞衍生的无细胞DNA（cfDNA）片段是具有生物活性的分子，可以轻易进入健康细胞以激活受体中的DNA损伤和凋亡反应。然而，传统上不知道DNA会自发进入细胞或具有任何固有的生物学活性。我们假设细胞进入和获得生物学特性是DNA大小的函数。为了验证这一假设，我们通过超声处理高分子量DNA（HMW DNA）模仿循环cfDNA生成了小DNA片段。从癌性和非癌性人类细胞，细菌和植物中分离出的HMW DNA进行超声处理，生成的片段大小为300-3000 bp，类似于报道的cfDNA循环片段。我们在这里表明，尽管HMW DNA无法进入细胞，但是来自不同来源的超声DNA（sDNA）可以不加区分地这样做，而无需注意物种或王国的边界。因此，来自人类细胞的sDNA以及来自细菌和植物的sDNA可以进入小鼠细胞核，而来自人，细菌和植物来源的sDNA可以自发进入细菌。细胞内的sDNA与宿主细胞染色体相关联并整合到其基因组中。此外，来自所有四个来源的sDNA而不是HMW DNA可以磷酸化H2AX并激活小鼠细胞中的促炎转录因子NFκB，这表明sDNA具有获得的生物学活性。我们的结果表明，来自不同来源的DNA小片段可以不加选择地跨物种和界界进入其他细胞，以整合到其基因组中并激活生物过程。这增加了以下可能性：通过充当参与水平基因转移的移动遗传元件，在有机细胞死亡后产生的片段化DNA可能具有进化意义。