美国一份研究揭示遏制DNA损伤的新线索
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美国一份研究揭示遏制DNA损伤的新线索


安德烈斯·阿奎莱拉(Andrés Aguilera)的实验室与拉尔夫·韦林格(Ralf Wellinger )均为塞维利亚大学CABIMER遗传学系教授和法瑪馬爾制藥公司(PharmaMar)的实验室合作,确定了两种天然化合物棒曲霉素(Patulina)和西斯托喹醇(Xestoquinol)作为拓扑异构酶1(Topoisomerase I)的新抑制剂,拓扑异构酶1是DNA正常运作的关键元素。该研究结果发表在《美国国家科学院院刊》(PNAS)上,为理解和治疗与遗传物质损伤相关的疾病打开了新的大门。

DNA拓扑酶1是一种广泛存在于所有生物体中的酶,对于细胞增殖是必不可少的。它的功能基于两个催化步骤:首先切割DNA,然后连接该切口,从而缓解在复制和转录期间产生的拓扑应力;还有第二个催化步骤抑制剂,它们可以防止DNA切口被重新分解,使其处于开放状态。因此可作为拓扑异构酶毒药,作为抗癌药物。

然而,尽管其具有在基础研究中的潜力及其在医学中的潜在应用,但尚无可靠的DNA切割第一步抑制剂。根据这项研究,棒曲霉素(Patulina)和西斯托喹醇(Xestoquinol)抑制了体外、酵母及人细胞中I型拓扑异构酶的第一次催化活性。

这项研究的主要作者是埃马努埃拉·图米尼(Emanuela Tumini)博士,该研究发表在美国国家科学院(Natl Acd Sci USA)´过程杂志´《Proc.》上,这表明发现了一类新型抑制剂,为基础研究和抗癌研究开辟了新视角。

这项研究主要得到国家研究机构挑战项目(RETOS)的资助。
E. Tumini, R.E. Wellinger, E. Herrera-Moyano, P. Navarro-Cansino, M. García-Rubio, D. Salas-Lloret, A. Losada, M.J. Muñoz-Alonso, H. Gaillard, R. Luna, & A. Aguilera, Patulin and Xestoquinol are inhibitors of DNA topoisomerase 1, Proc. Natl. Acad. Sci. U.S.A. 122 (17) e2421167122, (2025). DOI: 10.1073/pnas.2421167122
Regions: Europe, Spain
Keywords: Health, Medical, Science, Life Sciences

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