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TIP60 acetylation of Bub1 regulates centromeric H2AT120 phosphorylation for faithful chromosome segregation

science China life sciences 2024年第9期67卷 1957-1969页

作者： Mengjie Sun Biying Yang Guangwei Xin Yao Wang Jia Luo Qing Jiang Chuanmao Zhang The Academy for Cell and life Health Faculty of Life Science and Technology Kunming University of Science and Technology The Key laboratory of Cell Proliferation and Differentiation of the Ministry of Education College of Life Sciences Peking University

Proper function of the centromeres ensures correct attachment of kinetochores to spindle microtubules and faithful chromosome segregation in mitosis. Defects in the integrity and function of centromeres can result in chromosome missegregation and genomic ***1 is essential for the mitotic centromere dynamics, yet the underlying molecular mechanisms remain largely unclear. Here, we demonstrate that TIP60 acetylates Bub1 at K424 and K431 on kinetochores in early mitosis. This acetylation increases the kinase activity of Bub1 to phosphorylate centromeric histone H2A at T120(H2Ap T120), which recruits Aurora B and Shugoshin 1(Sgo1) to regulate centromere integrity, protect centromeric cohesion, and ensure the subsequent faithful chromosome segregation. Expression of the nonacetylated Bub1 mutant reduces its kinase activity, decreases the level of H2Ap T120, and disrupts the recruitment of centromere proteins and chromosome congression, leading to genomic instability of daughter cells. When cells exit mitosis, HDAC1-regulated deacetylation of Bub1 decreases H2Ap T120 levels and thereby promotes the departure of centromeric CPC and Sgo1, ensuring timely centromeres disassembly. Collectively, our results reveal a molecular mechanism by which the acetylation and deacetylation cycle of Bub1 modulates the phosphorylation of H2A at T120 for recruitment of Aurora B and Sgo1 to the centromeres, ensuring faithful chromosome segregation during mitosis.

关键词： acetylation Bub1 TIP60 H2ApT120 chromosome segregation

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Inhibition mechanisms of CRISPR-Cas9 by Acr ⅡA25.1 and AcrⅡA32

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science China life sciences 2024年第9期67卷 1781-1791页

作者： Jianlin Zheng Yuwei Zhu Tengjin Huang Wenbo Gao Jiale He Zhiwei Huang HIT Center for life sciences School of Life Science and Technology Harbin Institute of Technology Westlake Center for Genome Editing Westlake Laboratory of Life Sciences and Biomedicine School of Life Sciences Westlake University

In the ongoing arms race between bacteria and bacteriophages, bacteriophages have evolved anti-CRISPR proteins to counteract bacterial CRISPR-Cas systems. Recently, Acr ⅡA25.1 and Acr ⅡA32 have been found to effectively inhibit the activity of Spy Cas9 both in bacterial and human cells. However, their molecular mechanisms remain elusive. Here, we report the cryo-electron microscopy structures of ternary complexes formed by Acr ⅡA25.1 and Acr ⅡA32 bound to Spy Cas9-sg RNA. Using structural analysis and biochemical experiments, we revealed that Acr ⅡA25.1 and Acr ⅡA32 recognize a novel, previously-unidentified anti-CRISPR binding site on Spy Cas9. We found that both Acr ⅡA25.1 and Acr ⅡA32 directly interact with the WED domain, where they spatially obstruct conformational changes of the WED and PI domains, thereby inhibiting Spy Cas9 from recognizing protospacer adjacent motif(PAM) and unwinding double-stranded DNA. In addition,they may inhibit nuclease activity by blocking the dynamic conformational changes of the Spy Cas9 surveillance complex. In summary, our data elucidate the inhibition mechanisms of two new anti-CRISPR proteins, provide new strategies for the modulation of Spy Cas9 activity,and expand our understanding of the diversity of anti-CRISPR protein inhibition mechanisms.

关键词： anti-CRISPR cryo-EM SpyCas9 AcrIIA25.1 AcrIIA32 inhibiton

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Selenium-oxidizing Agrobacterium sp.T3F4 decreases arsenic uptake by Brassica rapa *** a native polluted soil

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Journal of Environmental sciences 2024年第4期138卷 506-515页

作者： Lijin An Chunzhi Zhou Lipeng Zhao Ao Wei Yiting Wang Huimin Cui Shixue Zheng State Key laboratory of Agricultural Microbiology College of Life Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China

Toxic arsenic(As)and trace element selenium(Se)are transformed by microorganisms but their complex interactions in soil-plant systems have not been fully *** Asand Se-oxidizing bacterium,Agrobacterium sp.T3F4,was applied to a native seleniferous As-polluted soil to investigate As/Se uptake by the vegetable Brassica rapa *** As-Se interaction as mediated by strain *** Se content in the aboveground plants was significantly enhanced by 34.1%,but the As content was significantly decreased by 20.5% in the T3F4-inoculated pot culture compared to the control(P<0.05).Similar result was shown in treatment with additional 5 mg/kg of Se(IV)in *** addition,the As contents in roots were significantly decreased by more than 35% under T3F4 or Se(IV)treatments(P<0.05).Analysis of As-Se-bacterium interaction in a soil simulation experiment showed that the bioavailability of Se significantly increased and As was immobilized with the addition of the T3F4strain(P<0.05).Furthermore,an As/Se co-exposure hydroponic experiment demonstrated that As uptake and accumulation in plants was reduced by increasing Se(IV)*** 50% growth inhibition concentration(IC50)values for As in plants were increased about one-fold and two-fold under co-exposure with 5 and 10μmol/L Se(IV),*** conclusion,strain T3F4 improves Se uptake but decreases As uptake by plants via oxidation of As and Se,resulting in decrease of soil As bioavailability and As/Se competitive absorption by *** provides a potential bioremediation strategy for Se biofortification and As immobilization in As-polluted soil.

关键词： Selenium oxidation Selenium biofortification Arsenite-oxidizing bacteria Arsenic immobilization Brassica rapa L

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Instantaneous preparation of gold-carbon dot nanocomposites for on-site SERS identification of pathogens in diverse interfaces

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Photonics Research 2024年第6期12卷 1303-1312页

作者： YANXIAN GUO YE LIU CHAOCAI LUO YUE ZHANG YANG LI FEI ZHOU ZHOUYI GUO ZHENGFEI ZHUANG ZHIMING LIU School of Electronic Engineering and Intelligentization Dongguan University of TechnologyDongguan 523808China Department of Physics University of Science and Technology of ChinaHefei 230026China MOE Key laboratory of Laser life science&Guangdong Provincial Key laboratory of Laser life science College of BiophotonicsSouth China Normal UniversityGuangzhou 510631China

Rapid detection of pathogens present on contaminated surfaces is crucial for food safety and public health due to the high morbidity and mortality of bacterial ***,a sensitive and efficient method for on-site identification of foodborne pathogens on anisotropic surfaces was developed by using an in situ instantaneously prepared surface-enhanced Raman scattering(SERS)*** achieve this,molybdenum-doped gallic acid-derived carbon dots(MCDs)are utilized as the reductant for synthesizing Au@MCDs nanohybrids within just 3 s at ambient *** synergistic effect of the electromagnetic enhancement and charge transfer of Au@MCDs enables excellent SERS performance 10 times stronger than bare Au *** bioassay platform requires less than 5 min to complete the quantitative detection of foodborne pathogens on various microbial-contaminated interfaces with a sensitivity of 10 CFU/*** innovative strategy breaks the long-standing limitations of SERS substrates in practical use,such as the time-consuming process,interference of residual surfactants,poor surface stability,and few application scenarios,providing a promising tool for widespread applications in biomedical research and clinical diagnostics.

关键词： temperature. molybdenum consuming

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Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

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National science Review 2024年第2期11卷 124-134页

作者： Jingyu Li Weibo Hou Qi Zhao Wei Han Hongdi Cui Songling Xiao Ling Zhu Jiadan Qu Xiaoyu Liu Weitao Cong Jingling Shen Yuzheng Zhao Shaorong Gao Guoning Huang Qingran Kong Chongqing Key laboratory of Human Embryo Engineering Center for Reproductive Medicine Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical University Oujiang laboratory Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life Sciences Wenzhou Medical University Frontier science Center for Stem Cell Research School of Life Sciences and Technology Tongji University School of Pharmaceutical science Wenzhou Medical University Institute of life sciences College of Life and Environmental Sciences Wenzhou University Optogenetics&Synthetic Biology Interdisciplinary Research Center State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology

Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation(ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-Co A and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

关键词： mammalian preimplantation development lactate epigenetic remodeling histone lactylation zygotic genome activation

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Tripartite motif-containing protein 11(TRIM11):a novel weapon against Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2024年第2期9卷 339-340页

作者： Yichu Fu Bi Zhang Jianfeng Liu College of life science and Technology Key Laboratory of Molecular Biophysics of MOEHuazhong University of Science and TechnologyWuhanHubei 430074China

In a recent study published in science,Zhang et *** that tripartite motif-containing(TRIM)protein 11(TRIM11)exhibited strong inhibition on tau aggregation,which is a pathological characteristic of tauopathies including Alzheimer’s disease(AD).1 This makes TRIM11 a promising novel target for the treatment of AD and other tauopathies.

关键词： Alzheimer tau TRIM

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Phosphorylation Promotes the Accumulation of PERIOD Protein Foci

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Research 2024年第1期2023卷 59-69页

作者： Mengna Li Shujing Li Luoying Zhang Key laboratory of Molecular Biophysics of Ministry of Education College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhanHubei 430074China Department of life sciences Bengbu Medical CollegeBengbuAnhui 233030China Hubei Province Key laboratory of Oral and Maxillofacial Development and Regeneration WuhanHubei 430022China

Circadian clock drives the 24-h rhythm in our behavior and *** molecular clock consists of a series of transcriptional/translational feedback loops operated by a number of clock genes.A very recent study reported that the clock protein PERIOD(PER)is organized into discrete foci at the nuclear envelope in fly circadian neurons,which is believed to be important for controlling the subcellular localization of clock *** of inner nuclear membrane protein lamin B receptor(LBR)leads to disruption of these foci,but how they are regulated is yet ***,we found that PER foci are likely phase-separated condensates,the formation of which is mediated by intrinsically disordered region in *** promotes the accumulation of these *** phosphatase 2A,which is known to dephosphorylate PER,hampers the accumulation of the *** the other hand,the circadian kinase DOUBLETIME(DBT)which phosphorylates PER enhances the accumulation of the *** likely facilitates PER foci accumulation by destabilizing the catalytic subunit of protein phosphatase 2A,MICROTUBULE STAR(MTS).In conclusion,here,we demonstrate a key role for phosphorylation in promoting the accumulation of PER foci,while LBR modulates this process by impinging on the circadian phosphatase MTS.

关键词： conclusion separated translational

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Nature-inspired design of droplet-synthesized polymeric nanoelectrode for photoelectrochemical microRNA sensing within single cells

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science Bulletin 2024年第2期69卷 159-162页

作者： Si-Yuan Yu Yi-Li Liu Zheng Li Dechen Jiang Jing-Juan Xu Hong-Yuan Chen Wei-Wei Zhao State Key laboratory of Analytical Chemistry for life science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China

Nanoelectrodes have been shown to be powerful tools for nanoscopic research on single entities,deepening the understanding of heterogeneity and stochastics for single molecules,nanoparticles and cells[1–3].However,despite their importance,current nanoelectrode preparations are highly restrained to flame/electrochemical etching,metal sputtering,electrochemical deposition,etc.[3],resulting in a limited range of materials(mainly gold,platinum and carbon)for potential-resolved detection of redox-active species(Table S1 online).The enrichment of preparation methods to introduce novel materials and mechanisms should prove significant for the development of nanoelectrodes.

关键词： electrode deepening restrained

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A practical guide for fast implementation of SNARE-mediated liposome fusion

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Biophysics Reports 2024年第1期10卷 31-40页

作者： Shen Wang Cong Ma Key laboratory of Molecular Biophysics of the Ministry of Education College of Life Science and TechnologyHuazhong University of Science and Technology

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor(SNAER) family proteins are the engines of most intra-cellular and exocytotic membrane fusion pathways(Jahn and Scheller 2006).Over the past two decades, in-vitro liposome fusion has been proven to be a powerful tool to reconstruct physiological SNARE-mediated membrane fusion processes(Liu et al. 2017). The reconstitution of the membrane fusion process not only provides direct evidence of the capability of the cognate SNARE complex in driving membrane fusion but also allows researchers to study the functional mechanisms of regulatory proteins in related pathways(Wickner and Rizo 2017). Heretofore, a variety of delicate methods for in-vitro SNARE-mediated liposome fusion have been established(Bao et al. 2018;Diao et al. 2012; Duzgunes 2003; Gong et al. 2015; Heo et al. 2021; Kiessling et al. 2015; Kreye et al.2008; Kyoung et al. 2013; Liu et al. 2017; Scott et al. 2003). Although technological advances have made reconstitution more physiologically relevant, increasingly elaborate experimental procedures, instruments, and data processing algorithms nevertheless hinder the non-experts from setting up basic SNARE-mediated liposome fusion assays. Here, we describe a low-cost, timesaving, and easy-to-handle protocol to set up a foundational in-vitro SNARE-mediated liposome fusion assay based on our previous publications(Liu et al. 2023; Wang and Ma 2022). The protocol can be readily adapted to assess various types of SNARE-mediated membrane fusion and the actions of fusion regulators by using appropriate alternative additives(e.g., proteins, macromolecules, chemicals, etc.). The total time required for one round of the assay is typically two days and could be extremely compressed into one day.

关键词： Liposome fusion SNARE In-vitro reconstitution Protocol

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TaSRO1 interacts with TaVP1 to modulate seed dormancy and pre-harvest sprouting resistance in wheat

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Journal of Integrative Plant Biology 2024年第1期66卷 36-53页

作者： Shupeng Liu Li Li Wenlong Wang Guangmin Xia Shuwei Liu Key laboratory of Plant Development and Environmental Adaptation Biology Ministry of EducationSchool of Life ScienceShandong UniversityQingdao 266237China

Dormancy is an adaptive trait which prevents seeds from germinating under unfavorable environmental *** with weak dormancy undergo pre-harvest sprouting(PHS)which decreases grain yield and *** the genetic mechanisms that regulate seed dormancy and resistance to PHS is crucial for ensuring global food *** this study,we illustrated the function and molecular mechanism of TaSRO1 in the regulation of seed dormancy and PHS resistance by suppressing *** tasro1 mutants exhibited strong seed dormancy and enhanced resistance to PHS,whereas the mutants of tavp1 displayed weak *** evidence has shown that TaVP1 is epistatic to *** evidence has shown that TaSRO1 interacts with TaVP1 and represses the transcriptional activation of the PHS resistance genes TaPHS1 and ***,TaSRO1 undermines the synergistic activation of TaVP1 and TaABI5 in PHS resistance ***,we highlight the great potential of tasro1 alleles for breeding elite wheat cultivars that are resistant to PHS.

关键词： wheat seed dormancy pre-harvest sprouting(PHS) ABA signaling vivipary

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