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自身DNA暴露会在……中引发发育缺陷和生殖系DNA损伤反应。

Self-DNA Exposure Induces Developmental Defects and Germline DNA Damage Response in .

作者信息

Germoglio Marcello, Adamo Adele, Incerti Guido, Cartenì Fabrizio, Gigliotti Silvia, Storlazzi Aurora, Mazzoleni Stefano

机构信息

Institute of Biosciences and BioResources, National Research Council, Via Pietro Castellino 111, 80131 Napoli, Italy.

Department of Agri-Food, Animal and Environmental Sciences (DI4A), University of Udine, 33100 Udine, Italy.

出版信息

Biology (Basel). 2022 Feb 8;11(2):262. doi: 10.3390/biology11020262.

Abstract

All organisms, from bacteria to mammals, sense and respond to foreign nucleic acids to fight infections in order to survive and preserve genome integrity across generations. The innate immune system is an evolutionarily conserved defence strategy. Complex organisms have developed various cellular processes to respond to and recognise not only infections, i.e., pathogen-associated molecular patterns (PAMPs), but also to sense injury and tissue dysfunctions, i.e., damage-associated molecular patterns (DAMPs). Mis-localized self-DNA can be sensed as DAMP by specific DNA-sensing pathways, and self-DNA chronic exposure can be detrimental to the organisms. Here, we investigate the effects of dietary delivered self-DNA in the nematode . The hermaphrodite worms were fed on genomic libraries: a library (self) and a legume () library (non-self). We show that the self-library diet affects embryogenesis, larval development and gametogenesis. DNA damage and activation of p53/CEP-1-dependent apoptosis occur in gonadal germ cells. Studies of self-DNA exposure in this model organism were not pursued up to now. The genetic tractability of will help to identify the basic molecular pathways involved in such mechanisms. The specificity of the adverse effects associated with a self-DNA enriched diet suggests applications in biological pest control approaches.

摘要

所有生物,从细菌到哺乳动物,都能感知并对外源核酸做出反应以对抗感染,从而生存并在世代间保持基因组完整性。先天免疫系统是一种进化上保守的防御策略。复杂生物已经发展出各种细胞过程,不仅对感染(即病原体相关分子模式,PAMPs)做出反应并识别,还能感知损伤和组织功能障碍(即损伤相关分子模式,DAMPs)。错误定位的自身DNA可通过特定的DNA感知途径被感知为DAMP,而自身DNA的长期暴露可能对生物有害。在这里,我们研究了线虫中饮食摄入的自身DNA的影响。雌雄同体的线虫被喂食基因组文库:一个文库(自身)和一个豆科植物文库(非自身)。我们发现自身文库饮食会影响胚胎发育、幼虫发育和配子发生。性腺生殖细胞中会发生DNA损伤和p53/CEP-1依赖性凋亡的激活。迄今为止,尚未对这种模式生物中自身DNA暴露进行研究。线虫的遗传易处理性将有助于确定参与此类机制的基本分子途径。与富含自身DNA的饮食相关的不良反应的特异性表明其在生物害虫控制方法中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75e5/8869574/95428d51c841/biology-11-00262-g001.jpg

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