目的活细胞在体分子之间或者分子内部力的定量测量是阐释其力学生物学规律的基础。目前具有可控几何形状的、特定阈值范围的DNA纳米结构力学探针是胞外受体-配体相互作用力在体测量的理想手段。但是,由于细胞铺展、迁移等生物学行为导...目的活细胞在体分子之间或者分子内部力的定量测量是阐释其力学生物学规律的基础。目前具有可控几何形状的、特定阈值范围的DNA纳米结构力学探针是胞外受体-配体相互作用力在体测量的理想手段。但是,由于细胞铺展、迁移等生物学行为导致的加载环境变化,DNA力学探针是否以及如何受到加载率等因素调控尚不清楚。方法本工作以一种生物素化的,具有4.2、12与19 p N 3种不同力学阈值的,可逆型DNA力学探针为对象,采用单分子原子力显微镜技术,通过设定不同回拉速率(100~1000 nm/s),定量考察不同加载率下力学探针的阈值分布以及生物素-链霉亲和素相互作用力的变化。结果通过空白对照、生物素阻断以及阳性条件下黏附概率的显著性差异,确定了实验体系的可行性与可靠性。实验测量获得的3种探针力学阈值分布与其标定值相当。随着回拉速率的增加,3种DNA力学探针阈值分布无明显变化,而生物素-链霉亲和素之间的相互作用则随着回拉速率逐渐增加。结论本工作表明加载率对可逆型DNA力学探针与受体-配体相互作用的不同调控作用,为深入理解其作用机制提供基础数据。展开更多
生命系统具有鲜明的非平衡性,能量耗散是其典型特征。基于DNA纳米技术,科学家们正不断开发着更接近于生命系统的化学传感器[1]。为生命体的自组装研究提供了新的视角,在材料、生物医学和工程等领域具有重要应用价值。最近,新南威尔士大...生命系统具有鲜明的非平衡性,能量耗散是其典型特征。基于DNA纳米技术,科学家们正不断开发着更接近于生命系统的化学传感器[1]。为生命体的自组装研究提供了新的视角,在材料、生物医学和工程等领域具有重要应用价值。最近,新南威尔士大学的Jonathon E.Beves和Felix J.Rizzuto团队研究了可见光和小分子对于DNA基序寿命的影响,其研究成果发表在Journal of the American Chemical Society杂志上[2](J.Am.Chem.Soc.2023,145,2088-2092)。展开更多
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
文摘目的活细胞在体分子之间或者分子内部力的定量测量是阐释其力学生物学规律的基础。目前具有可控几何形状的、特定阈值范围的DNA纳米结构力学探针是胞外受体-配体相互作用力在体测量的理想手段。但是,由于细胞铺展、迁移等生物学行为导致的加载环境变化,DNA力学探针是否以及如何受到加载率等因素调控尚不清楚。方法本工作以一种生物素化的,具有4.2、12与19 p N 3种不同力学阈值的,可逆型DNA力学探针为对象,采用单分子原子力显微镜技术,通过设定不同回拉速率(100~1000 nm/s),定量考察不同加载率下力学探针的阈值分布以及生物素-链霉亲和素相互作用力的变化。结果通过空白对照、生物素阻断以及阳性条件下黏附概率的显著性差异,确定了实验体系的可行性与可靠性。实验测量获得的3种探针力学阈值分布与其标定值相当。随着回拉速率的增加,3种DNA力学探针阈值分布无明显变化,而生物素-链霉亲和素之间的相互作用则随着回拉速率逐渐增加。结论本工作表明加载率对可逆型DNA力学探针与受体-配体相互作用的不同调控作用,为深入理解其作用机制提供基础数据。
文摘红藻真江蓠(Gracilaria vermiculophylla)是西北太平洋地区特有种,但在过去100年间它借助海运(太平洋牡蛎养殖)快速入侵到北美、欧洲和地中海等沿海栖息地,对当地的生物多样性、海洋环境和生态系统等造成重大影响。为从分子水平初步了解真江蓠成功入侵的潜在机制,文章对其入侵起源地——日本北部的真江蓠及非入侵种——绳状龙须菜(Gracilariopsis chorda)进行了同质园实验(common garden experiment)处理后的比较转录组研究,以探究该地区入侵属性不同的两种红藻间的基因表达差异。结果表明,真江蓠和绳状龙须菜共有基因序列集(Universal Gene,unigene)主要集中在核糖体、嘌呤和嘧啶代谢等通路。其中,在真江蓠中光系统II反应中心蛋白D1(photosystem II reaction center protein D1)、细胞色素P450单加氧酶(cytochrome P450 monooxygenase)和核酮糖1,5二磷酸羧化酶大亚基(Ribulose bisphosphate carboxylase large subunit,rbcL)等基因的表达量显著上调,而逆转录转座子蛋白(retrotransposon protein)、细胞壁相关的水解酶(cell wall-associated hydrolase)和金属离子转运蛋白Nramp5的表达既上调也下调。与光合作用过程相关基因的大量表达可能有助于真江蓠应对逆境胁迫,特别是光系统ⅡD1反应中心蛋白表达量升高可能有助于藻体修复光系统Ⅱ复合体,从而制造更多的有机物以备藻体生长所需。而金属离子转运蛋白Nramp5等的上调和下调则表明江蓠等红藻可能通过某些基因表达量的增减对不同的环境变动作出响应。总体而言,代谢过程中的资源再分配很可能是驱动真江蓠适应和耐受新的生境的主要分子机制。
文摘生命系统具有鲜明的非平衡性,能量耗散是其典型特征。基于DNA纳米技术,科学家们正不断开发着更接近于生命系统的化学传感器[1]。为生命体的自组装研究提供了新的视角,在材料、生物医学和工程等领域具有重要应用价值。最近,新南威尔士大学的Jonathon E.Beves和Felix J.Rizzuto团队研究了可见光和小分子对于DNA基序寿命的影响,其研究成果发表在Journal of the American Chemical Society杂志上[2](J.Am.Chem.Soc.2023,145,2088-2092)。
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.
