PLANT JOURNAL
·
2018
·Vol. 94
·期 2
·288-303
·
IF 5.775
Jie Qian,Yueyue Chen,Ying Hu,Yingtian Deng,Yang Liu,Gang Li,Wenxuan Zou,Jie Zhao
Summary Replication factor C (RFC) is a conserved eukaryotic complex consisting of RFC1/2/3/4/5. It plays important roles in DNA replication and the cell cycle in yeast and fruit fly. However, it is not very clear how RFC subunits function in higher plants, except for the Arabidopsis ( At ) subunits AtRFC1 and AtRFC3 . In this study, we investigated the functions of AtRFC4 and found that loss of function of AtRFC4 led to an early sporophyte lethality that initiated as early as the elongated zygote stage, all defective embryos arrested at the two- to four-cell embryo proper stage, and the endosperm possessed six to eight free nuclei. Complementation of rfc4-1 /+ with AtRFC4 expression driven through the embryo-specific DD45pro and ABI3pro or the endosperm-specific FIS2pro could not completely restore the defective embryo or endosperm, whereas a combination of these three promoters in rfc4-1 /+ enabled the aborted ovules to develop into viable seeds. This suggests that AtRFC4 functions simultaneously in endosperm and embryo and that the proliferation of endosperm is critical for embryo maturation. Assays of DNA content in rfc4-1 /+ verified that DNA replication was disrupted in endosperm and embryo, resulting in blocked mitosis. Moreover, we observed a decreased proportion of late S-phase and M-phase cells in the rfc4-1 /– FIS 2; DD 45; ABI 3pro::At RFC 4 seedlings, suggesting that incomplete DNA replication triggered cell cycle arrest in cells of the root apical meristem. Therefore, we conclude that AtRFC4 is a crucial gene for DNA replication.
研究领域:
植物学
·
遗传学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-10
·
IF 5.228
Huang Wuren,Zhang Jie,Yang Bing,Beerntsen Brenda T.,Song Hongsheng,Ling Erjun
Invertebrate animals have the capacity of repairing wounds in the skin and gut via different mechanisms. Gastrointestinal perforation, a hole in the human gastrointestinal system, is a serious condition and surgery is necessary to repair the perforation to prevent an abdominal abscess or sepsis. Here we report the repair of gastrointestinal perforation made by a needle-puncture wound in the silkworm larval midgut. Following insect gut perforation, only a weak immune response was observed because the growth of Escherichia coli alone was partially inhibited by plasma collected at 6 h after needle puncture of the larval midgut. However, circulating hemocytes did aggregate over the needle-puncture wound to form a scab. While, cell division and apoptosis were not observed at the wound site, the needle puncture significantly enhanced DNA duplication in cells surrounding the wound, which was essential to repair the midgut perforation. Due to the repair capacity and limited immune response caused by needle puncture to the midgut, this approach was successfully used for the injection of small compounds (ethanol in this study) into the insect midgut. Consequently, this needle-puncture wounding of the insect gut can be developed for screening compounds for use as gut chemotherapeutics in the future.
研究领域:
昆虫学
·
医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLS TISSUES ORGANS
·
2022
·
IF 2.208
Zhou Yafu,Yan Jianhua,Chen Huiguo,Zhou Wenwu,Yang Jinsong
GINS subunit complex 4 (GINS4) is fundamental to DNA replication and G1/S phase transition of the cell cycle in eukaryotes. Further, recent studies implied that GINS4 can mediate the progression of several tumors, but its mechanism in lung adenocarcinoma (LUAD) is not clarified. Therefore, the role of GINS4 in LUAD was explored. miR-133a-3p and GINS4 mRNA expression were tested through qRT-PCR. Protein levels of the two genes were assayed by Western blot. Their targeting relationship was predicted and verified by bioinformatics prediction and dual-luciferase analysis. The functions of miR-133a-3p and GINS4 in LUAD were evaluated by Transwell, wound healing, CCK-8, and flow cytometry assays. MTT assay and caspase-3 activity detection were utilized to measure the regulation of miR-133a-3p/GINS4 in the cisplatin sensitivity of LUAD cells. The results showed that GINS4 was highly expressed in LUAD cells (p < 0.05). miR-133a-3p, the upstream gene of GINS4 in LUAD, negatively mediated GINS4 expression. Moreover, overexpressing GINS4 enhanced the proliferative, migratory, and invasive abilities of LUAD cells and inhibited cell apoptosis and the sensitivity to cisplatin, while overexpressing miR-133a-3p caused the contrary results. However, the promoting effects of GINS4 overexpression on LUAD could be offset by miR-133a-3p overexpression. miR-133a-3p could regulate malignant behaviors and cisplatin sensitivity of LUAD cells through negatively regulating GINS4. In conclusion, our findings demonstrated that GINS4 was overexpressed in LUAD and promoted the malignant behavior of LUAD cells. Moreover, miR-133a-3p could negatively regulate GINS4, thereby suppressing the malignant progression and increasing the cisplatin sensitivity of LUAD
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Haibo Zhang,Lizhi Li,Gangfu Chen,Nancheng Yin,Jiangao Guo,Xinrui Ni,Yixin Liu,Ke Wu,Weikun Guan,Cheng Zhang,Xiaochun Wu,Shi Wenkai,Qingfeng Xing,Dongsheng Guo
The existence of Antibiotic Resistance Genes (ARGs) in diverse everyday environments, such as animal agriculture, natural surroundings, and waste products, presents potential threats to both human health and food safety. Herein, metagenomic sequencing technique was employed to investigate the impact of two zinc-based nanoparticles , Graphene Oxide-modified Zinc Oxide (GOnZnO) and Microorganism-mediated Zinc Oxide (Micro-ZnO), on the microbial community , ARGs, and DNA replication. The results showed that both GOnZnO and Micro-ZnO significantly reduced zinc levels in animal manure when compared to the control group of nano zinc oxide (nZnO). The order of ARGs copy numbers was nZnO > GOnZnO > Micro-ZnO, with a significant difference between the GOnZnO and Micro-ZnO groups. Additionally, the expression levels of various DNA replication genes, including DNA polymerase III holoenzyme , dnaB , dnaG , RNeseH , polA , and Lig , were significantly lower in the GOnZnO group compared to the nZnO group. The Micro-ZnO group exhibited even lower expression levels of these genes compared to the GOnZnO group. In contrast, GOnZnO and Micro-ZnO had no significant impact on archaeal DNA replication pathway-related genes. Specifically, the expression of RNASEH1 was significantly higher in the Micro-ZnO group compared to the GOnZnO and nZnO groups. Co-occurrence network analysis revealed changes in ARGs driven by bacterial and eukaryotic DNA replication and microbial community dynamics. However, there was no correlation observed between ARGs and archaeal DNA replication genes. Overall, these findings add to the existing literature regarding the application of GOnZnO and Micro-ZnO as potential agents for reducing ARGs pollution.
研究领域:
环境科学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2020
·
IF 3.184
Yuhe Kan,Lu Chen,Dao Lin,Xinya Bu,Mengwu Mo,Liang Yan,Zhenjun Yang,Longfei Yuan,Li Wu,Yujian He
DNA damage can occur naturally or through environmental factors, leading to mutations in DNA replication and genomic instability in cells. Normally, natural d-nucleotides were selected by DNA polymerases. The template l-thymidine (l-T) has been shown to be bypassed by several types of DNA polymerases. However, DNA replication fidelity of nucleotide incorporation opposite l-thymidine in vivo remains unknown. Here, we constructed plasmids containing a restriction enzyme (PstI) recognition site in which the l-T lesion was site-specifically located within the PstI recognition sequence (CTGCAG). Further, we assessed the efficiencies of nucleotide incorporation opposite the l-T site and l-T lesion bypass replication in vitro and in vivo. We found that recombinants containing the l-T lesion site inhibited DNA replication. In addition, A was incorporated opposite the l-T lesion by routine PCR assay, whereas preference for nucleotide incorporation opposite the l-T site was A (13%), T (22%), C (46%), and G (19%), and no nucleotide insertion and deletions were detected in E. coli cells. In particular, a novel restriction enzyme-mediated method for detection of the mutagenic properties of DNA lesion was established, which allows us to readily detect restriction–digestion of the l-T-bearing plasmids. The study provided significant insight into how mirror-image nucleosides perturb the fidelity of DNA replication in vivo and whether they elicit mutagenic effects, which may help to understand both how DNA damage interferes with the flow of genetic information during DNA replication and development of diseases caused by gene mutation.
研究领域:
分子生物学
·
遗传学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 18
·8626-8634
·
IF 5.396
Fengzhi Qiao,Xiaoting Yu,Shanshan Tie,Yannan Chen,Shuai Hou,Mingqian Tan
Food-borne nanoparticles from Undaria pinnatifida (UPFNs) were prepared and successfully applied as nanocarriers for microelement zinc delivery. UPFNs were spherical nanoparticles with average sizes of about 4.07 ± 1.09 nm, which chelated with zinc ions through amino nitrogen and carboxyl oxygen atoms as characterized by X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance spectroscopy. Thermodynamic analysis revealed that the overall chelation process between UPFNs and zinc ions was a spontaneous enthalpy-driven endothermic reaction. Compared to zinc sulfate, UPFN–Zn2+ showed higher solubility both in phytic acid solution and the process of gastrointestinal digestion. Meanwhile, no obvious cytotoxicity was found in UPFNs and UPFN–Zn2+. Specifically, UPFN–Zn2+ could successfully rescue cell viability, DNA replication activity and restore cell proliferation ability in zinc-deficient cells induced by a specific zinc chelator TPEN. Overall, UPFNs might serve as efficient, stable, and safe nanocarriers for zinc delivery.
研究领域:
纳米技术
·
营养学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Min Hou,Hou Cong Li,Ning An,Si Yan Pang,Wen Ge Li,Jing Tong
Three metal complexes [Ni 2 (HL) 2 (C 2 H 5 OH) 2 Cl 2 ]·2C 2 H 5 OH (complex 1), [Co (HL) (L)] (complex 2) and [Zn 2 (HL) 2 (CH 3 COO) 2 ] (complex 3) derived from 5-bromosalicylaldehyde-2-(2-aminophenyl)benzimidazole Schiff base ligand (H 2 L) were synthesized and characterized by infrared (IR) spectroscopy, thermogravimetric (TG) analysis and powder X-ray diffraction (XRD). Single crystal X-ray diffraction analysis confirmed that complex 1 crystallized in binuclear octahedral structure with space group P2 1 /C and complex 2 displayed in mononuclear octahedral structure with space group P 121/c 1. While complex 3 produced binuclear pyramid structure with space group P 121/c 1. Herein, cobalt (Ⅱ) salt was oxidized to form Schiff base cobalt (Ⅲ) complex by coordinating three deprotonated groups. The MTT method was employed to determine the three complexes in vitro cytotoxicity effects against human lung cancer cells (A-549), liver cancer cells (SMMC-7721), breast cancer cells (MDA-MB-231) and nasopharyngeal carcinoma cells (CNE-2Z). The results showed that Co (Ⅲ) complex has significant anticancer activity against human breast cancer MDA-MB-231 cells compared with cisplatin. The further study of its anticancer mechanisms exhibited that Co (Ⅲ) complex could inhibit MDA-MB-231 cells proliferation through both apoptosis and DNA replication inhibition.
研究领域:
无机化学
·
药物化学
·
肿瘤学
✓ 已验证
DOI
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 26
·6123-6130
·
IF 7
E Pang,Xuejian Xing,Shaojing Zhao,Qiuxia Tan,Tangna Pan,Ting Yu,Yabing Gan,Benhua Wang,Siyi Tan,Yi Zhang,Peng Yin,Xiangzhi Song,Minhuan Lan
Sonodynamic therapy (SDT) has emerged as a promising treatment approach of solid tumors given its deep tissue penetration, non-invasiveness, few side effects, and negligible drug resistance. Herein, we report the first polythiophene derivative-based sonosensitizer (PT2) containing a quaternary ammonium salt and dodecyl chains with better ultrasound stability than that of traditional sonosensitizers, such as Rose Bengal and chlorin e6. PT2 was encapsulated by folic acid-containing polyethylene glycol. The obtained nanoparticles (PDPF NPs) exhibited excellent biocompatibility, cancer cell-targeting capacity, and accumulated mainly in the lysosomes and plasma membranes of cells. These NPs could generate singlet oxygen and superoxide anions simultaneously under ultrasound irradiation. In vitro and in vivo experimental results demonstrated that PDPF NPs could induce cancer-cell death through apoptosis and necrosis, inhibit DNA replication, and ultimately achieve tumor depletion upon US irradiation. These findings revealed that polythiophene could serve as an efficacious sonosensitizer for enhanced US treatment of deep-seated tumors.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2025
·Vol. 16
·期 1
·1-14
·
IF 9.6
Liu Min,Li Yuanyuan,Deng Zhilin,Zhang Ke,Huang Shuying,Xia Jiamin,Feng Yi,Liang Yundan,Sun Chengfu,Liu Xindong,Li Shurong,Su Bingyin,dong Yong,Huang Sizhou
Mutation in genes involved in DNA replication continuously disrupt DNA replication and give rise to genomic instability, a critical driver of oncogenesis. To prevent leukemia, immature T lymphocytes with genomic instability often undergo rapid cell death during development. However, the mechanism by which immature T lymphocytes undergo rapid cell death upon genomic instability has been enigmatic. Here we show that zebrafish mcm5 mutation leads to DNA damage in immature T lymphocytes and the immature T cells sensitively undergo rapid cell death. Detailed analyses demonstrated that the immature T lymphocytes undergo rapid apoptosis via upregulation of tp53 and downregulation of bcl2 transcription in mcm5 mutants. Mechanistically, Mcm5 directly binds to Stat1a and facilitates its phosphorylation to enhance bcl2a expression under the conditions of DNA replication stress. However, in mcm5 mutants, the absence of the Mcm5-Stat1 complex decreases Stat1 phosphorylation and subsequent bcl2a transcription, accelerating apoptosis of immature T lymphocytes with genomic instability. Furthermore, our study shows that the role of Mcm5 in T-cell development is conserved in mice. In conclusion, our work identifies a role of Mcm5 in regulating T cell development via Stat1-Bcl2 cascade besides its role in DNA replication, providing a kind of mechanism by which immature T cells with gene mutation-induced DNA damage are rapidly cleared during T lymphocyte development.
研究领域:
免疫学
·
遗传学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Physical Chemistry Letters
·
2022
·
IF 6.888
Xianjing Zhang,Zhi Zhu,Wenpeng Liu,Feng Gao,Jun Guo,Bo Song,Luke P. Lee,Feng Zhang
Metal ions play vital roles in the electron transfer between biological molecules in humans, animals, and plants. However, the electron transfer between metal ions and nucleic acids and its impact on DNA–ion binding during DNA replication has been ignored. Here, we present a long-range quantum biological electron transfer (QBET) between DNA bases and metal ions and its selective function of DNA–ion binding in DNA replication. We discover biophysical DNA–ion binding and create biological filters that allow selective DNA replication by dual modulators of the valence and concentration of metal ions. QBET-based DNA replication filters provide powerful tools for ultrasensitive polymerase chain reaction (PCR) to selectively amplify target sequences with a discrete concentration window of metal ions; for example, Au3+ exhibits a concentration window that is approximately 3 orders of magnitude lower than that of Na+. DNA–ion filters provide new perspectives into metal ion-mediated QBET in DNA replication and hold great potential in life sciences and medical applications.
研究领域:
生物物理学
·
分子生物学
·
量子生物学
·
生物无机化学
·
遗传学
✓ 已验证
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2023
·
IF 14.5
Xiaowei Wang,Mengyan Wang,Meilian Cai,Rongguang Shao,Guimin Xia,Wuli Zhao
Pancreatic cancer is a more aggressive and refractory malignancy. Resistance and toxicity limit drug efficacy. Herein, we report a lower toxic and higher effective miriplatin (MPt)-loaded liposome, LMPt, exhibiting totally different anti-cancer mechanism from previously reported platinum agents. Both in gemcitabine (GEM)-resistant/sensitive (GEM-R/S) pancreatic cancer cells, LMPt exhibits prominent anti-cancer activity, led by faster cellular entry-induced larger accumulation of MPt. The level of caveolin-1 (Cav-1) determines entry rate and switch of entry pathways of LMPt, indicating a novel role of Cav-1 in nanoparticle entry. After endosome-lysosome processing, in unchanged metabolite, MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM, to degrade POLG and TFAM. Then, via PINK1-Parkin axis, mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA (mtDNA) replication blocking. Additionally, POLG and TFAM are identified as novel prognostic markers of pancreatic cancer, and mtDNA replication-induced mitophagy blocking mediates their pro-cancer activity. Our findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA (target of most platinum agents), and totally distinct mechanism of MPt and other formulations of MPt. Self-assembly offers LMPt special efficacy and mechanisms. Prominent action and characteristic mechanism make LMPt a promising cancer candidate.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Xin Peng,Xin Huang,Shaolu Zhang,Naixin Zhang,Shengfan Huang,Yingying Wang,Zhenxing Zhong,Shan Zhu,Haiwang Gao,Zixiang Yu,Xiaotong Yan,Zhennan Tao,Yuxiang Dai,Zhe Zhang,Xi Chen,Feng Wang,Francois X. Claret,Moshe Elkabets,Ning Ji,Yuxu Zhong,Dexin Kong
PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair. Through in vitro experiments using established GBM cell lines and patient-derived primary GBM cells, as well as in vivo orthotopic transplantation tumor experiments in zebrafish and nude mice, it is demonstrated that the concurrent administration of PARPi and BETi can synergistically inhibit GBM. Intriguingly, it is observed that DNA damage lingers after discontinuation of PARPi monotherapy, implying that sequential administration of PARPi followed by BETi can maintain antitumor efficacy while reducing toxicity. In GBM cells with elevated baseline replication stress, the sequential regimen exhibits comparable efficacy to concurrent treatment, protecting normal glial cells with lower baseline replication stress from DNA toxicity and subsequent death. This study provides compelling preclinical evidence supporting the development of innovative drug administration strategies focusing on PARPi for GBM therapy.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）