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Causal genetic regulation of DNA replication on immune microenvironment in colorectal tumorigenesis: Evidenced by an integrated approach of trans-omics and GWAS
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作者 Sumeng Wang Silu Chen +6 位作者 Huiqin Li Shuai Ben Tingyu Zhao Rui Zheng Meilin Wang Dongying Gu Lingxiang Liu 《The Journal of Biomedical Research》 CAS CSCD 2024年第1期37-50,共14页
The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant... The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets. 展开更多
关键词 trans-omics dna replication tumor immune microenvironment causal mediation colorectal tumorigenesis
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Transcriptional regulation of secondary metabolism and autophagy genes in response to DNA replication stress in Setosphaeria turcica
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作者 MENG Ya-nan ZHANG Xin-jie +8 位作者 ZENG Fan-li ZHAI Wei-bo LI Pan HU Jing-jing XIAO Sheng-lin HAO Zhi-min CAO Zhi-yan CHEN Chuan DONG Jin-gao 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2023年第4期1068-1081,共14页
The fungal pathogen Setosphaeria turcica causes northern corn leaf blight(NCLB),which leads to considerable crop losses.Setosphaeria turcica elaborates a specialized infection structures called appressorium for maize ... The fungal pathogen Setosphaeria turcica causes northern corn leaf blight(NCLB),which leads to considerable crop losses.Setosphaeria turcica elaborates a specialized infection structures called appressorium for maize infection.Previously,we demonstrated that the S.turcica triggers an S-phase checkpoint and ATR(Ataxia Telangiectasia and Rad3 related)-dependent self-protective response to DNA genotoxic insults during maize infection.However,how the regulatory mechanism works was still largely unknown.Here,we report a genome wide transcriptional profile analysis during appressorium formation in the present of DNA replication stress.We performed RNA-Seq analysis to identify S.tuicica genes responsive to DNA replication stress.In the current work,we found that appressorium-mediated maize infection by S.turcica is significantly blocked by S-phase checkpoint.A large serial of secondary metabolite and melanin biosynthesis genes were blocked in appressorium formation of S.turcica during the replication stress.The secondary metabolite biosynthesis genes including alcohol dehydrogenase GroES-like domain,multicopper oxidase,ABCtransporter families,cytochrome P450 and FAD-containing monooxygenase were related to plant pathogen infection.In addition,we demonstrated that autophagy in S.turcica is up-regulated by ATR as a defense response to stress.We identified StATG3,StATG4,StATG5,StATG7 and StATG16 genes for autophagy were induced by ATR-mediated S-phase checkpoint.We therefore propose that in response to genotoxic stress,S.turcica utilizes ATR-dependent pathway to turn off transcription of genes governing appressorium-mediated infection,and meanwhile inducing transcription of autophagy genes likely as a mechanism of self-protection,aside from the more conservative responses in eukaryotes. 展开更多
关键词 Setosphaeria turcica APPRESSORIUM secondary metabolite AUTOPHAGY dna replication stress
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Melanin,DNA replication,and autophagy affect appressorium development in Setosphaeria turcica by regulating glycerol accumulation and metabolism 被引量:3
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作者 GUO Xiao-yue LIU Ning +4 位作者 LIU Bing-hui ZHOU Li-hong CAO Zhi-yan HAN Jian-min DONG Jin-gao 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2022年第3期762-773,共12页
Setosphaeria turcica(syn.Exserohilum turcicum)is the pathogenic fungus of maize(Zea mays)that causes northern leaf blight,which is a major maize disease worldwide.Melanized appressoria are highly specialized infection... Setosphaeria turcica(syn.Exserohilum turcicum)is the pathogenic fungus of maize(Zea mays)that causes northern leaf blight,which is a major maize disease worldwide.Melanized appressoria are highly specialized infection structures formed by germinated conidia of S.turcica that infect maize leaves.The appressorium penetrates the plant cuticle by generating turgor,and glycerol is known to be the main source of the turgor.Here,the infection position penetrated by the appressorium on maize leaves was investigated,most of the germinated conidia entered the leaf interior by directly penetrating the epidermal cells,and the appressorium structure was necessary for the infection,whether it occurred through epidermal cells or stomata.Then,to investigate the effects of key factors in the development of the appressorium,we studied the effects of three inhibitors,including a melanin inhibitor(tricyclazole,TCZ),a DNA replication inhibitor(hydroxyurea,HU),and an autophagy inhibitor(3-methyladenine,3-MA),on appressorium turgor and glycerol content.As results,appressorium turgor pressure and glycerol concentration in the appressorium reached their highest levels at the mature stage of the appressorium under the control and inhibitor treatments.The three inhibitors had the greatest effects on appressorium turgor pressure at this stage.Glycogen and liposomes are the main substances producing glycerol.It was also found inhibitors affected the distribution of glycogen and liposomes,which were detected in the conidia,the germ tube,and the appressorium during appressorium development.This study provides profound insight into the relationship between appressorium turgor pressure and glycerol content,which was affected by the synthesis of melanin,DNA replication,and autophagy in the developing appressorium during a S.turcica infection. 展开更多
关键词 MELANIN dna replication AUTOPHAGY APPRESSORIUM DEVELOPMENT Setosphaeria turcica GLYCEROL
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Artesunate Reduces Proliferation, Interferes DNA Replication and Cell Cycle and Enhances Apoptosis in Vascular Smooth Muscle Cells 被引量:3
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作者 周志明 冯义柏 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2005年第2期135-136,177,共3页
Summary: This study examined the effect of artesunate (Art) on the proliferation, DNA replication, cell cycles and apoptosis of vascular smooth muscle cells (VSMCs). Primary cultures of VSMCs were established from aor... Summary: This study examined the effect of artesunate (Art) on the proliferation, DNA replication, cell cycles and apoptosis of vascular smooth muscle cells (VSMCs). Primary cultures of VSMCs were established from aortas of mice and artesunate of different concentrations was added into the medium. The number of VSMCs was counted and the curve of cell growth was recorded. The activity of VSMCs was assessed by using MTT method and inhibitory rate was calculated. DNA replication was evaluated by [3H]-TdR method and apoptosis by DNA laddering and HE staining. Flowmetry was used for simultaneous analysis of cell apoptosis and cell cycles. Compared with the control group, VSMCs proliferation in Art interfering groups were inhibited and [3H]-TdR incorprating rate were decreased as well as cell apoptosis was induced. The progress of cell cycle was blocked in G 0/G 1 by Art in a dose-dependent manner. It is concluded that Art inhibits VSMCs proliferation by disturbing DNA replication, inducing cell apoptosis and blocking cell cycle in G 0/G 1 phase. 展开更多
关键词 PROLIFERATION dna replication cell cycle APOPTOSIS smooth muscle
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Differential activation of intra-S-phase checkpoint in response to tripchlorolide and its effects on DNA replication 被引量:2
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作者 YanREN JiaRuiWU 《Cell Research》 SCIE CAS CSCD 2004年第3期227-233,共7页
DNA replication is tightly regulated during the S phase of the cell cycle, and the activation of the intra-S-phase checkpoint due to DNA damage usually results in arrest of DNA synthesis. However, the molecular detail... DNA replication is tightly regulated during the S phase of the cell cycle, and the activation of the intra-S-phase checkpoint due to DNA damage usually results in arrest of DNA synthesis. However, the molecular details about the correlation between the checkpoint and regulation of DNA replication are still unclear. To investigate the connections between DNA replication and DNA damage checkpoint, a DNA-damage reagent, tripchlorolide, was applied to CHO (Chinese ovary hamster) cells at early- or middle-stages of the S phase. The early-S-phase treatment with TC significantly delayed the progression of the S phase and caused the phosphorylation of the Chkl checkpoint protein, whereas the middle-S-phase treatment only slightly slowed down the progression of the S phase. Furthermore, the analysis of DNA replication patterns revealed that replication pattern II was greatly prolonged in the cells treated with the drug during the early-S phase, whereas the late-replication patterns of these cells were hardly detected, suggesting that the activation of the intra-S-phase checkpoint inhibits the late-origin firing of DNA replication. We conclude that cells at different stages of the S phase are differentially sensitive to the DNA-damage reagent, and the activation of the intra-S phase checkpoint blocks the DNA replication progression in the late stage of S phase. 展开更多
关键词 intra-S-phase checkpoint dna replication dna damage tripchlorolide.
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AcMNPV As A Model for Baculovirus DNA Replication
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作者 Eric B. Carstens 《Virologica Sinica》 SCIE CAS CSCD 2009年第4期243-267,共25页
Baculoviruses were first identified as insect-specific pathogens, and it was this specificity that lead to their use as safe, target specific biological pesticides. For the past 30 years, AcMNPV has served as the subj... Baculoviruses were first identified as insect-specific pathogens, and it was this specificity that lead to their use as safe, target specific biological pesticides. For the past 30 years, AcMNPV has served as the subject of intense basic molecular research into the baculovirus infectious cycle including the interaction of the virus with a continuous insect cell line derived from Spodoptera frugiperda. The studies on baculoviruese have led to an in-depth understanding of the physical organization of the viral genomes including many complete genomic sequences, the time course of gene expression, and the application of this basic research to the use of baculoviruses not only as insecticides, but also as a universal eukaryotic protein expression system, and a potential vector in gene therapy. A great deal has also been discovered about the viral genes required for the replication of the baculovirus genome, while much remains to be learned about the mechanism of viral DNA replication. This report outlines the current knowledge of the factors involved in baculovirus DNA replication, using data on AcMNPV as a model for most members of the Baculoviridae. 展开更多
关键词 BACULOVIRUS dna replication ACMNPV Molecular virology REVIEW
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Regulation of eukaryotic DNA replication and nuclear structure
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作者 WU JIA RUI(Shanghai Institute of Biochemistry, Chinese Academy ofSciences Shanghai 200031, China)e-mail: wwir@sunm.shcnc. ac. cn 《Cell Research》 SCIE CAS CSCD 1999年第3期163-170,共8页
In eukaryote, nuclear structure is a key component forthe functions of eukaryotic cells. More and more evidencesshow that the nuclear structure plays important role in re-gulating DNA replication. The nuclear structur... In eukaryote, nuclear structure is a key component forthe functions of eukaryotic cells. More and more evidencesshow that the nuclear structure plays important role in re-gulating DNA replication. The nuclear structure providesa physical barrier for the replication licensing, participatesin the decision where DNA replication initiates, and orga-nizes replication proteins as replication factory for DNAreplication. Through these works, new concepts on theregulation of DNA replication have emerged, which willbe discussed in this minireview. 展开更多
关键词 dna replication nuclear structure replication licensing replication origin replication factory
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Acceleration of DNA Replication of Klenow Fragment by Small Resisting Force
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作者 Yu-Ru Liu Peng-Ye Wang +1 位作者 Wei Li Ping Xie 《Chinese Physics Letters》 SCIE CAS CSCD 2021年第11期91-95,共5页
DNA polymerases are an essential class of enzymes or molecular motors that catalyze processive DNA syntheses during DNA replications. A critical issue for DNA polymerases is their molecular mechanism of processive DNA... DNA polymerases are an essential class of enzymes or molecular motors that catalyze processive DNA syntheses during DNA replications. A critical issue for DNA polymerases is their molecular mechanism of processive DNA replication. We have proposed a model for chemomechanical coupling of DNA polymerases before, based on which the predicted results have been provided about the dependence of DNA replication velocity upon the external force on Klenow fragment of DNA polymerase I. Here, we performed single molecule measurements of the replication velocity of Klenow fragment under the external force by using magnetic tweezers. The single molecule data verified quantitatively the previous theoretical predictions, which is critical to the chemomechanical coupling mechanism of DNA polymerases. A prominent characteristic for the Klenow fragment is that the replication velocity is independent of the assisting force whereas the velocity increases largely with the increase of the resisting force,attains the maximum velocity at about 3.8 pN and then decreases with the further increase of the resisting force. 展开更多
关键词 dna Acceleration of dna replication of Klenow Fragment by Small Resisting Force
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Essential functions of iron-requiring proteins n DNA replication, repair and cell cycle contro 被引量:17
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作者 Caiguo Zhang 《Protein & Cell》 SCIE CAS CSCD 2014年第10期750-760,共11页
Eukaryotic cells contain numerous iron-requiring pro- teins such as iron-sulfur (Fe-S) cluster proteins, hemoproteins and ribonucleotide reductases (RNRs). These proteins utilize iron as a cofactor and perform key... Eukaryotic cells contain numerous iron-requiring pro- teins such as iron-sulfur (Fe-S) cluster proteins, hemoproteins and ribonucleotide reductases (RNRs). These proteins utilize iron as a cofactor and perform key roles in DNA replication, DNA repair, metabolic catalysis, iron regulation and cell cycle progression. Disruption of iron homeostasis always impairs the functions of these iron- requiring proteins and is genetically associated with diseases characterized by DNA repair defects in mam- mals. Organisms have evolved multi-layered mecha- nisms to regulate iron balance to ensure genome stability and cell development. This review briefly pro- vides current perspectives on iron homeostasis in yeast and mammals, and mainly summarizes the most recent understandings on iron-requiring protein functions involved in DNA stability maintenance and cell cycle control. 展开更多
关键词 iron-requiring protein dna replication dna repair cell cycle iron homeostasis
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Demonstration of biophoton-driven DNA replication via gold nanoparticle-distance modulated yield oscillation 被引量:6
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作者 Na Li Daoling Peng +4 位作者 Xianjing Zhang Yousheng Shu Feng Zhang Lei Jiang Bo Song 《Nano Research》 SCIE EI CAS CSCD 2021年第1期40-45,共6页
Biologically,there exist two kinds of syntheses:photosynthesis and ATP-driven biosynthesis.The light harvesting of photosynthesis is known to achieve an efficiency of〜95%by the quantum energy transfer of photons.Howev... Biologically,there exist two kinds of syntheses:photosynthesis and ATP-driven biosynthesis.The light harvesting of photosynthesis is known to achieve an efficiency of〜95%by the quantum energy transfer of photons.However,how the ATP-driven biosynthesis reaches its high efficiency still remains unknown.Deoxynucleotide triphosphates(dNTPs)in polymerase chain reaction(PCR)adopt the identical way of ATP to release their energy,and thus can be employed to explore the ATP energy process.Here,using a gold nanoparticle(AuNP)enhanced PCR(AuNP-PCR),we demonstrate that the energy released by phosphoanhydride-bond(PB)hydrolysis of dNTPs is in form of photons(PB-photons)to drive DNA replication,by modulating their resonance with the average inter-AuNP distance(D).The experimental results show that both the efficiency and yield of PCR periodically oscillate with D increasing,indicating a quantized process,but not simply a thermal one.The PB-photon wavelength is further determined to 8.4 pm.All these results support that the release,transfer and utilization of bioenergy are in the form of photons.Our findings of ATP-energy quantum conversion will open a new avenue to the studies of high-efficiency bioenergy utilization,biochemistry,biological quantum physics,and even brain sciences. 展开更多
关键词 intrinsic biophoton dna replication polymerase chain reaction(PCR) gold nanoparticle high-efficiency energy utilization biological quantum physics
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A Combined Computational and Experimental Study on the Structure-Regulation Relationships of Putative Mammalian DNA Replication Initiator GINS 被引量:4
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作者 Reiko Hayashi Takako Arauchi +2 位作者 Moe Tategu Yuya Goto Kenichi Yoshida 《Genomics, Proteomics & Bioinformatics》 SCIE CAS CSCD 2006年第3期156-164,共9页
GINS, a heterotetramer of SLD5, PSF1, PSF2, and PSF3 proteins, is an emerging chromatin factor recognized to be involved in the initiation and elongation step of DNA replication. Although the yeast and Xenopus GINS ge... GINS, a heterotetramer of SLD5, PSF1, PSF2, and PSF3 proteins, is an emerging chromatin factor recognized to be involved in the initiation and elongation step of DNA replication. Although the yeast and Xenopus GINS genes are well documented, their orthologous genes in higher eukaryotes are not fully characterized. In this study, we report the genomic structure and transcriptional regulation of mammalian GINS genes. Serum stimulation increased the GINS mRNA levels in human cells. Reporter gene assay using putative GINS promoter sequences revealed that the expression of mammalian GINS is regulated by 17β-Estradiolstimulated estrogen receptor a, and human PSF3 acts as a gene responsive to transcription factor E2F1. The goal of this study is to present the current data so as to encourage further work in the field of GINS gene regulation and functions in mammalian cells. 展开更多
关键词 dna replication initiation bioinformatics gene structure gene regulation 17Β-ESTRADIOL transcription factor E2F1
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Mechanism of chromosomal DNA replication initiation and replication fork stabilization in eukaryotes 被引量:3
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作者 WU LiHong LIU Yang KONG DaoChun 《Science China(Life Sciences)》 SCIE CAS 2014年第5期482-487,共6页
Chromosomal DNA replication is one of the central biological events occurring inside cells. Due to its large size, the replica-tion of genomic DNA in eukaryotes initiates at hundreds to tens of thousands of sites call... Chromosomal DNA replication is one of the central biological events occurring inside cells. Due to its large size, the replica-tion of genomic DNA in eukaryotes initiates at hundreds to tens of thousands of sites called DNA origins so that the replication could be completed in a limited time. Further, eukaryotic DNA replication is sophisticatedly regulated, and this regulation guarantees that each origin fires once per S phase and each segment of DNA gets duplication also once per cell cycle. The first step of replication initiation is the assembly of pre-replication complex (pre-RC). Since 1973, four proteins, Cdc6/Cdcl8, MCM, ORC and Cdtl, have been extensively studied and proved to be pre-RC components. Recently, a novel pre-RC compo- nent called Sapl/Girdin was identified. Sapl/Girdin is required for loading Cdcl8/Cdc6 to origins for pre-RC assembly in the fission yeast and human cells, respectively. At the transition of G1 to S phase, pre-RC is activated by the two kinases, cy- clin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK), and subsequently, RPA, primase-polct, PCNA, topoisomer-ase, Cdc45, polδ and pole are recruited to DNA origins for creating two bi-directional replication forks and initiating DNA replication. As replication forks move along chromatin DNA, they frequently stall due to the presence of a great number of replication barriers on chromatin DNA, such as secondary DNA structures, protein/DNA complexes, DNA lesions, gene tran-scription. Stalled forks must require checkpoint regulation for their stabilization. Otherwise, stalled forks will collapse, which results in incomplete DNA replication and genomic instability. This short review gives a concise introduction regarding the current understanding of replication initiation and replication fork stabilization. 展开更多
关键词 dna replication origins pre-RC assembly replication fork stability S phase checkpoint
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HPV18 DNA replication inactivates the early promoter P_(55) activity and prevents viral E6 expression 被引量:1
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作者 Xiaohong Wang Haibin Liu +3 位作者 Hsu-Kun Wang Craig Meyers Louise Chow Zhi-Ming Zheng 《Virologica Sinica》 SCIE CAS CSCD 2016年第5期437-440,共4页
Dear Editor,Human papillomaviruses(HPV)are a large group(>200genotypes)of small double-stranded DNA viruses(https://pave.niaid.nih.gov/).Although infections by most HPV types are asymptomatic,persistent infections ... Dear Editor,Human papillomaviruses(HPV)are a large group(>200genotypes)of small double-stranded DNA viruses(https://pave.niaid.nih.gov/).Although infections by most HPV types are asymptomatic,persistent infections in cervical and ano-genital epithelia by high-risk 展开更多
关键词 HPV18 dna replication inactivates the early promoter P dna activity and prevents viral E6 expression
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Rapid progress of DNA replication studies in Archaea,the third domain of life
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作者 ISHINO Yoshizumi ISHINO Sonoko 《Science China(Life Sciences)》 SCIE CAS 2012年第5期386-403,共18页
Archaea,the third domain of life,are interesting organisms to study from the aspects of molecular and evolutionary biology.Archaeal cells have a unicellular ultrastructure without a nucleus,resembling bacterial cells,... Archaea,the third domain of life,are interesting organisms to study from the aspects of molecular and evolutionary biology.Archaeal cells have a unicellular ultrastructure without a nucleus,resembling bacterial cells,but the proteins involved in genetic information processing pathways,including DNA replication,transcription,and translation,share strong similarities with those of Eukaryota.Therefore,archaea provide useful model systems to understand the more complex mechanisms of genetic information processing in eukaryotic cells.Moreover,the hyperthermophilic archaea provide very stable proteins,which are especially useful for the isolation of replisomal multicomplexes,to analyze their structures and functions.This review focuses on the history,current status,and future directions of archaeal DNA replication studies. 展开更多
关键词 ARCHAEA dna replication dna polymerase replication fork REPLISOME HYPERTHERMOPHILE
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5-Formyluracil targeted biochemical reactions with proteins inhibit DNA replication,induce mutations and interference gene expression in living cells
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作者 Guangrong Zou Kaiyuan Zhang +3 位作者 Wei Yang Chaoxing Liu Zhentian Fang Xiang Zhou 《Chinese Chemical Letters》 SCIE CAS CSCD 2021年第10期3252-3256,共5页
Covalent DNA–protein cross-links are toxic DNA lesions that interfere with essential biological processes,which can cause serious biological consequences,such as genomic instability and protein misexpression.5-Formyl... Covalent DNA–protein cross-links are toxic DNA lesions that interfere with essential biological processes,which can cause serious biological consequences,such as genomic instability and protein misexpression.5-Formyluracil(5 fU) as an important modification in DNA,which is mainly from oxidative damage,exists in a variety of cells and tissues.We have reported that 5 fU mediated DNA–protein conjugates could exist in human cells [Zhou et al.CCS Chem.2(2020) 54–63].We now aimed to explore its potential biological effects in vitro and in vivo.In this paper,we firstly reported that 5 fU intermediated DNA–peptide or DNA–protein conjugates(both were called DPCs) could inhibit different polymerases bypass or cause mutations.Then we further investigated the functional impacts caused by 5 fU-mediated DPCs,which appeared in different gene expression components [in the promoter sequence or 50-untranslated regions(UTR)].These results together may contribute to a broader understanding of DNA–protein interactions as well as the biological functions associated with 5 fU. 展开更多
关键词 5-Formyluracil Biochemicalreaction dna replication Mutation Gene expression
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Next-generation sequencing-based analysis of the effect of N^(6)-methyldeoxyadenosine modification on DNA replication in human cells
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作者 Juan Wang Yuwei Sheng +2 位作者 Ying Yang Xiaoxia Dai Changjun You 《Chinese Chemical Letters》 SCIE CAS CSCD 2022年第4期2077-2080,共4页
N^(6)-methyldeoxyadenosine(6 mdA) modification is considered as a new epigenetic mark that may play important roles in various biological processes.However,it remains unclear about the effect of 6 mdA on DNA replicati... N^(6)-methyldeoxyadenosine(6 mdA) modification is considered as a new epigenetic mark that may play important roles in various biological processes.However,it remains unclear about the effect of 6 mdA on DNA replication in human cells.Herein,we combined next-generation sequencing with shuttle vector technology to explore how 6 mdA affects the efficiency and accuracy of DNA replication in human cells.Our results showed that 6 mdA neither blocked DNA replication nor induced mutations in human cells.Moreover,we found that the depletion of translesion synthesis DNA polymerase(Pol) κ,Pol η,Pol ι or Pol ζ did not significantly change the biological consequences of 6 mdA during replication in human cells.The negligible impact of 6 mdA on DNA replication is consistent with its potential role in epigenetic gene expression. 展开更多
关键词 N^(6)-methyldeoxyadenosine dna replication Next-generation sequencing Shuttle vector technology Translesion synthesis dna polymerase
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DNA replication components as regulators of epigenetic inheritance---lesson from fission yeast centromere
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作者 Haijin He Marlyn Gonzalez +1 位作者 Fan Zhang Fei Li 《Protein & Cell》 SCIE CAS CSCD 2014年第6期411-419,共9页
Genetic information stored in DNA is accurately copied and transferred to subsequent generations through DNA replication. This process is accomplished through the concerted actions of highly conserved DNA replication ... Genetic information stored in DNA is accurately copied and transferred to subsequent generations through DNA replication. This process is accomplished through the concerted actions of highly conserved DNA replication components. Epigenetic information stored in the form of histone modifications and DNA methylation, constitutes a second layer of regulatory information important for many cellular processes, such as gene expression regulation, chromatin organization, and genome stabil- ity. During DNA replication, epigenetic information must also be faithfully transmitted to subsequent generations. How this monumental task is achieved remains poorly understood. In this review, we will discuss recent advances on the role of DNA replication components in the inheritance of epigenetic marks, with a particular focus on epigenetic regulation in fission yeast. Based on these findings, we propose that specific DNA replication components function as key regulators in the replication of epigenetic information across the genome. 展开更多
关键词 epigenetic inheritance dna replication centromere histone modification heterochromatin euchromatin
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DNA replication licensing control and rereplication prevention
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作者 Chonghua Li Jianping Jin 《Protein & Cell》 SCIE CSCD 2010年第3期227-236,共10页
Eukaryotic DNA replication is tightly restricted to onlyonce per cell cycle in order to maintain genome stability.Cells use multiple mechanisms to control the assemblyof the prereplication complex (pre-RC), a process ... Eukaryotic DNA replication is tightly restricted to onlyonce per cell cycle in order to maintain genome stability.Cells use multiple mechanisms to control the assemblyof the prereplication complex (pre-RC), a process knownas replication licensing. This review focuses on theregulation of replication licensing by posttranslationalmodifications of the licensing factors, including phosphorylation, ubiquitylation and acetylation. These modifications are critical in establishing the pre-RCcomplexes as well as preventing rereplication in each cellcycle. The relationship between rereplication and diseases, including cancer and virus infection, is discussedas well. 展开更多
关键词 dna replication licensing REreplication protein modification
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RPA functions as a platform for coupling of nucleosome assembly to DNA replication
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《Science Foundation in China》 CAS 2017年第2期19-19,共1页
Subject Code:C05 With the support by the National Natural Science Foundation of China,the research team led by Dr.Li Qing(李晴)at the State Key Laboratory of Protein and Plant Gene Research,School of Life Sciences and... Subject Code:C05 With the support by the National Natural Science Foundation of China,the research team led by Dr.Li Qing(李晴)at the State Key Laboratory of Protein and Plant Gene Research,School of Life Sciences and Peking-Tsinghua Center for Life Sciences,Peking University,Beijing,recently reported that 展开更多
关键词 RPA functions as a platform for coupling of nucleosome assembly to dna replication dna
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Epigallocatechin gallate inhibits HBV DNA synthesis in a viral replication-inducible cell line 被引量:8
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作者 Wei He Li-Xia Li Qing-Jiao Liao Chun-Lan Liu Xu-Lin Chen 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第11期1507-1514,共8页
AIM:To analyze the antiviral mechanism of Epigallocatechin gallate(EGCG)against hepatitis B virus(HBV) replication.METHODS:In this research,the HBV-replicating cell line HepG2.117 was used to investigate the antiviral... AIM:To analyze the antiviral mechanism of Epigallocatechin gallate(EGCG)against hepatitis B virus(HBV) replication.METHODS:In this research,the HBV-replicating cell line HepG2.117 was used to investigate the antiviral mechanism of EGCG.Cytotoxicity of EGCG was analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Hepatitis B virus e antigen(HBeAg)and hepatitis B virus surface antigen(HBsAg)in the supernatant were detected by enzyme-linked immunosorbent assay.Precore mRNA and pregenomic RNA(pgRNA) levels were determined by semi-quantitative reverse transcription polymerase chain reaction(PCR)assay.The effect of EGCG on HBV core promoter activity was measured by dual luciferase reporter assay.HBV covalently closed circular DNA and replicative intermediates of DNA were quantified by real-time PCR assay.RESULTS:When HepG2.117 cells were grown in the presence of EGCG,the expression of HBeAg was suppressed,however,the expression of HBsAg was not affected.HBV precore mRNA level was also downregulated by EGCG,while the transcription of precore mRNA was not impaired.The synthesis of both HBV covalently closed circular DNA and replicative intermediates of DNA were reduced by EGCG treatment to a similar extent,however,HBV pgRNA transcripted from chromosome-integrated HBV genome was not affected by EGCG treatment,indicating that EGCG targets only replicative intermediates of DNA synthesis.CONCLUSION:In HepG2.117 cells,EGCG inhibits HBV replication by impairing HBV replicative intermediates of DNA synthesis and such inhibition results in reduced production of HBV covalently closed circular DNA. 展开更多
关键词 Covalently closed circular dna Epigallocatechin gallate Hepatitis B virus e antigen Hepatitis B virus Precore mRNA Replicative intermediates of dna
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