G-quadruplex(G4)is one of the higher-order DNA structures in guanine-rich sequences which are widely distributed across the genome.Due to their presence in oncogenic promoters and telomeres,G4 DNA structures become th...G-quadruplex(G4)is one of the higher-order DNA structures in guanine-rich sequences which are widely distributed across the genome.Due to their presence in oncogenic promoters and telomeres,G4 DNA structures become the novel targets in anticancer drug designs.Curaxin CBL0137,as an important candidate anticancer drug,can effectively inhibit the growth of multiple cancers.Although there is evidence that anticancer activity of curaxin is associated with its ability to bind DNA and to change the DNA topology,its therapeutic target and the underlying anti-cancer mechanism are still unclear.Here we show,for the first time,that curaxin CBL0137 induces G4 folding from anti-parallel to parallel structures,by single-molecule fluorescence resonance energy transfer technique.More importantly,we find that curaxin CBL0137 promotes G4 folding as well as stabilizes the folded G4 structures with long loops,giving a novel insight into effects of curaxin CBL0137 on DNA structures.Our work provides new ideas for the therapeutic mechanism of curaxin CBL0137 and for designs of new G4-targeting anticancer drugs.展开更多
据Lebrette H 2023年10月6日[Science,2023,382(6666):109-113.]报道,瑞典斯德哥尔摩大学、法国国家科学研究中心和美国劳伦斯伯克利国家实验室等研究机构的研究人员揭示了产生DNA构成单元的核糖核苷酸还原酶(ribonucleotide reductase,...据Lebrette H 2023年10月6日[Science,2023,382(6666):109-113.]报道,瑞典斯德哥尔摩大学、法国国家科学研究中心和美国劳伦斯伯克利国家实验室等研究机构的研究人员揭示了产生DNA构成单元的核糖核苷酸还原酶(ribonucleotide reductase,RNR)的神秘面纱。展开更多
基金supported by financial support from the National Key Research and Development Program of China(2021YFF1200200)the National Natural Science Foundation of China(22161132008)+2 种基金the Natural Science Foundation of Shanghai,China(19520714100 and 19ZR1475800)the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SNZJU-SIAS-006)the Natural Science Foundation of Zhejiang Province(LQ21C050001)。
基金supported by the National Natural Science Foundation of China(Grant Nos.10225417,21991133,12122402,and 12074043)the National Basic Research Program of China(Grant No.2006CB601003)。
文摘G-quadruplex(G4)is one of the higher-order DNA structures in guanine-rich sequences which are widely distributed across the genome.Due to their presence in oncogenic promoters and telomeres,G4 DNA structures become the novel targets in anticancer drug designs.Curaxin CBL0137,as an important candidate anticancer drug,can effectively inhibit the growth of multiple cancers.Although there is evidence that anticancer activity of curaxin is associated with its ability to bind DNA and to change the DNA topology,its therapeutic target and the underlying anti-cancer mechanism are still unclear.Here we show,for the first time,that curaxin CBL0137 induces G4 folding from anti-parallel to parallel structures,by single-molecule fluorescence resonance energy transfer technique.More importantly,we find that curaxin CBL0137 promotes G4 folding as well as stabilizes the folded G4 structures with long loops,giving a novel insight into effects of curaxin CBL0137 on DNA structures.Our work provides new ideas for the therapeutic mechanism of curaxin CBL0137 and for designs of new G4-targeting anticancer drugs.
文摘据Lebrette H 2023年10月6日[Science,2023,382(6666):109-113.]报道,瑞典斯德哥尔摩大学、法国国家科学研究中心和美国劳伦斯伯克利国家实验室等研究机构的研究人员揭示了产生DNA构成单元的核糖核苷酸还原酶(ribonucleotide reductase,RNR)的神秘面纱。
