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1.
Disaster Med Public Health Prep ; : 1-17, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32228732

RESUMO

BACKGROUND: As an emerging infectious disease, COVID-19 has involved with many countries and regions. With the further development of the epidemic, the proportion of clusters has been increased. METHODS: In our study, we collected the information of COVID-19 clusters in Qingdao City. The epidemiological characteristic and clinical manifestation were analyzed. RESULTS: 11 clusters of COVID-19 were reported in Qingdao City during Jan 29, 2020 and Feb 23, 2020, involved 44 confirmed cases, which were accounted for 73.33% of all confirmed cases. Most from Jan 19 and Feb 2, 2020, the cases mainly concentrated in the district which had many designated hospitals. The cases aged 20-59 years old accounted for the largest proportion (68.18%), with the male-to-female sex ration 0.52:1. Three cases were infected from exposure to confirmed cases. The average incubation period was 6.28d. The median number of cases per cluster was 4 and the median duration time was 6d.The median cumulative number of exposure persons was 53. CONCLUSION: More attention should be paid on the epidemic of clusters in prevention and control of COVID-19. Besides isolating patients, it is essential to track, screen and isolate the close contacts. Self-isolation is the key especially for healthy people in epidemic area.

2.
J Appl Microbiol ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32215987

RESUMO

AIM: The aim of this study was to evaluate the ability of Bacillus methylotrophicus M4-1 to protect winter wheat from the harmful effects of soil salinity and alkalinity. METHODS AND RESULTS: We isolated the halotolerant B. methylotrophicus M4-1. Two representative soils with different salt contents (S1, 213 µs·cm-1 ; S2, 786 µs·cm-1 ) in the Yellow River delta region of China were selected for experiments. The effects of the M4-1 strain on the typical wheat variety (Jimai 21) in this environment were proven. In S1 soil, the M4-1 strain reduced the wheat rhizosphere soil pH (1.61%) and electrical conductivity (EC) (8.01%) and increased the exchangeable K content (11.14%). The uptake of Mg2+ (20.73%) by wheat roots and K+ (8.84%) by leaves was increased, and the content of Na+ (23.62%) in leaves was reduced. In S2 soil, the M4-1 strain was able to reduce soil EC (2.56%) and increase exchangeable K (11.20%) content. The absorption of K+ (13.28%) in wheat leaves was increased, and the content of Na+ (12.41%) in roots was decreased. Total N and organic matter contents in rhizosphere soil were significantly positively correlated with wheat growth and salt tolerance, whereas EC showed a significant negative correlation. CONCLUSIONS: M4-1 attenuates salt stress injury in wheat under both low and high salt stress. SIGNIFICANCE AND IMPACT OF THE STUDY: We demonstrated the efficacy and value of plant growth-promoting rhizobacteria addition to protect winter wheat against salt stress and improve crop yield. We also elucidated the physicochemical and biochemical interactions among M4-1, the rhizosphere, and the host plant.

3.
Exp Biol Med (Maywood) ; : 1535370220911604, 2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32148090
4.
Int J Mol Sci ; 21(5)2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32155727

RESUMO

The plant-special SHI-RELATED SEQUENCE (SRS) family plays vital roles in various biological processes. However, the genome-wide analysis and abiotic stress-related functions of this family were less reported in soybean. In this work, 21 members of soybean SRS family were identified, which were divided into three groups (Group I, II, and III). The chromosome location and gene structure were analyzed, which indicated that the members in the same group may have similar functions. The analysis of stress-related cis-elements showed that the SRS family may be involved in abiotic stress signaling pathway. The analysis of expression patterns in various tissues demonstrated that SRS family may play crucial roles in special tissue-dependent regulatory networks. The data based on soybean RNA sequencing (RNA-seq) and quantitative Real-Time PCR (qRT-PCR) proved that SRS genes were induced by drought, NaCl, and exogenous abscisic acid (ABA). GmSRS18 significantly induced by drought and NaCl was selected for further functional verification. GmSRS18, encoding a cell nuclear protein, could negatively regulate drought and salt resistance in transgenic Arabidopsis. It can affect stress-related physiological index, including chlorophyll, proline, and relative electrolyte leakage. Additionally, it inhibited the expression levels of stress-related marker genes. Taken together, these results provide valuable information for understanding the classification of soybean SRS transcription factors and indicates that SRS plays important roles in abiotic stress responses.

5.
Oncol Lett ; 19(4): 3111-3122, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32218862

RESUMO

Lung cancer is the leading cause of cancer-associated mortality worldwide. In China, in particular, lung cancer mortality has markedly increased and is likely to continue to rise. RNA-binding proteins are pivotal to the development and progression of a variety of cancer types, including non-small cell lung cancer (NSCLC). RNA-binding motif protein 47 (RBM47) has been found to act as a tumor suppressor in breast cancer and NSCLC. However, to the best of our knowledge, RBM47 expression in NSCLC tissues has yet to be investigated. Analysis via the online database, Gene Expression Omnibus, revealed that RBM47 was upregulated in NSCLC and associated with pathological type, suggesting that RBM47 may play different roles in lung adenocarcinoma and lung squamous cell carcinoma. In the present study, the expression of RBM47 was examined by immunohistochemistry in 175 pairs of tumor and adjacent non-cancerous tissues resected from patients with NSCLC. The results indicated that the expression of RBM47 was significantly increased in NSCLC samples compared with that in the matched non-cancerous samples. Furthermore, RBM47 expression was higher in Xuanwei compared with that in non-Xuanwei NSCLC, suggesting that RBM47 is a more sensitive biomarker in Xuanwei NSCLC, and that it may serve as a candidate therapeutic target. In addition, RBM47 expression was associated with the pathological type, however not with the age, sex, lymph node metastasis, pT stage or pathological Tumor-Node-Metastasis stage of the patients. The increased expression level of RBM47 may indicate a worse overall survival rate for patients with NSCLC. In addition, multivariate survival analysis showed that the Xuanwei area is associated with poor prognosis for patients with NSCLC. In conclusion, the present study revealed that the upregulation of RBM47 accelerated the malignant progression of NSCLC, indicating that RBM47 may be a potential biomarker for NSCLC progression and a therapeutic target for NSCLC.

6.
Drug Des Devel Ther ; 14: 1145-1156, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214800

RESUMO

Background: Shenjin Huoxue Mixture (SHM), a classic traditional herb mixture has shown significant clinical efficacy against osteoarthritis (OA). Our previous experimental study has confirmed its anti-inflammatory and analgesic effect on acute soft tissue injury in rats, with the compound of glycyrrhizinate in SHM identified and the content of paeoniflorin in SHM determined by high-performance liquid chromatography (HPLC). However, the components and its pharmacological mechanisms of SHM against OA have not been systematically elucidated yet. Thus this study aimed to predict the key active ingredients and potential pharmacological mechanisms of SHM in the treatment of OA by network pharmacology approach and thin-layer chromatography (TLC) validation. Methods: The active ingredients of SHM and their targets, as well as OA-related targets, were identified from databases. The key active ingredients were defined and ranked by the number of articles retrieved in PubMed using the keyword "(the active ingredients [Title/Abstract]) AND Osteoarthritis[Title/Abstract] ", and validated partially by TLC. The pharmacological mechanisms of SHM against OA were displayed by GO term and Reactome pathway enrichment analysis with Discovery Studio 3.0 software docking to testing the reliability. Results: Finally, 16 key active ingredients were identified and ranked, including quercetin validated through TLC. Inflammatory response, IL-6 signaling pathway and toll-like receptor (TLR) cascades pathway were predicted as the main pharmacological mechanisms of SHM against OA. Especially, 12 out of 16 key active ingredients, including validated quercetin, were well docked to IL-6 proteins. Conclusion: Our results confirmed the anti-inflammatory and analgesic effect of SHM against OA through multiple components, multiple targets and multiple pathways, which revealed the theoretical basis of SHM against OA and may provide a new drug option for treating OA.

7.
Chemosphere ; 252: 126443, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32182509

RESUMO

Chlorinated polyfluoroalkyl ether sulfonates (trade name F-53B) has been detected in various environmental matrices, and reported to be equally or more toxic than perfluorooctane sulfonate. Efficient sorptive removal of F-53B from water by two types of layered double hydroxides (LDHs), NO3--LDH and sodium dodecyl sulfate modified NO3--LDH (SDS-LDH), was demonstrated in this study. Both LDHs removed F-53B in several minutes and had sorption capacities of over 860 mg/g. SDS-LDH exhibited a greater F-53B uptake than NO3--LDH under the influence of different solution chemistry, including pH 3-11, or in the presence of competing anions or co-contaminants, primarily due to the higher surface areas and the presence of SDS for SDS-LDH. Batch experiments, structural characterization, molecular dynamics simulations, and density functional theory calculations were combined to explore the sorption mechanisms, which mainly include ion exchange (specifically, O-H⋯O/F hydrogen bond), C-F/Cl⋯H hydrogen bond, and micellar sorption (occurring at high initial F-53B concentrations). Accordingly, we propose to improve the sorption performance of LDHs by increasing their surface areas and modifying LDHs to produce more hydrogen bond sites, as well as exfoliating LDHs into two dimensional nanosheets to eliminate the steric hindrance for the micellar formation of F-53B or other per- and polyfluoroalkyl substances.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32102388

RESUMO

To explore the joint toxicity and bio-accumulation of multi-heavy metals and potential chemoprevention strategies, Male Sprague Dawley (SD) rats (n = 30) were treated orally once a week for six months with 500mg/kg•bw of eight heavy metals which were commonly identified in aquatic products in the Ningbo area including chromium, manganese, nickel, copper, zinc, cadmium, mercury, and lead. At the same time, 200mg/kg•bw of epigallocatechin-3-gallate (EGCG), trisodium citrate dihydrate (TCD) or glutathione (GSH) were administered to evaluate their antagonistic effects against adverse effects of multi-heavy metal mixture. The Morris water maze test was used to evaluate spatial learning and memory in the treated rats. Then the rats were anesthetized by pentobarbital sodium (40 mg/kg•bw) to obtain blood samples for biochemical analysis and organs (heart, liver, spleen, lungs, kidneys, brain, testis) to be conducted for biopsy and organ coefficients. Inductively coupled plasma mass spectrometer (ICP-MS) was used to analyze the concentrations of heavy metals. Results indicated that six months of exposure to a multi-heavy metal mixture under this experimental dosage resulted in accumulation in organs and adverse effects on the blood, reproductive system, and liver function. EGCG, TCD or GSH all showed certain chemoprevention effects against the joint toxicity induced by the multi-heavy metal mixture and indicated alleviation and the potential mechanism that also included the promotion of excretion of metals to which animals were exposed.

9.
Bioengineered ; 11(1): 261-271, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32098576

RESUMO

Lung cancer patients with lymph node metastasis usually had short overall survival and occurred distant metastases at the early stage. However, some of these people did have more prolonged survival. The underlying reason is still unclear. In this study, we found a novel molecule, family with sequence similarity 136, member A gene (FAM136A). First, we performed immunohistochemistry for FAM136A in 177 lung carcinoma tissues. Second, we carried out in vitro studies by using A549 and PC-9. We detected FAM136A immunoreactivity in 79 out of 177 (44.6%) lung carcinoma tissues, and the FAM136A status was significantly associated with tumor T stage, lymph node metastasis, and the Tumor-Node-Metastasis (TNM) staging system in these cases. Importantly, it was significantly associated with the overall survival of the patients with lymph node metastasis, especially FAM136A positive patients, who had worse outcomes. Subsequent in vitro experiments revealed that the proliferation activity and migration property decreased both A549 and PC-9 lung carcinoma cells transfected with siRNA-FAM136A, and apoptosis reduced. Meanwhile, the expression of CDK4 and CDK6 decreased. FAM136A status would be a potent, worse prognostic factor in lung cancer patients with lymph node metastasis. It would play a vital role in the proliferation, apoptosis, and migration properties of A549 and PC-9. In the future, We will focus on the uncovered signal mechanism between FAM136A and lung cancer.

10.
Org Lett ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009410

RESUMO

A simple imine-based covalent organic framework (COF) as heterogeneous ligand for PdII-promoted Heck reaction is reported. Good regioselectivity for a wide range of electronically unbiased olefins is obtained (linear/branched >100:1 in most cases). Related tests and density functional theory calculations are used to explore the reason underlying the high selectivity. This research opens a route for COF as an intriguing platform to control regioselectivity catalysis.

11.
Int J Mol Sci ; 21(3)2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32050573

RESUMO

Salt stress inhibits normal plant growth and development by disrupting cellular water absorption and metabolism. Therefore, understanding plant salt tolerance mechanisms should provide a theoretical basis for developing salt-resistant varieties. Here, we cloned ThTrx5 from Tamarix hispida, a salt-resistant woody shrub, and generated ThTrx5-overexpressing transgenic Arabidopsis thaliana lines. Under NaCl stress, the germination rate of overexpressing ThTrx5 lines was significantly increased relative to that of the nontransgenic line; under salt stress, superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione levels and root length and fresh weight values of transgenic ThTrx5 plants were significantly greater than corresponding values for wild-type plants. Moreover, with regard to the transcriptome, comparison of differential gene expression of transgenic versus nontransgenic lines at 0 h and 3 h of salt stress exposure revealed 500 and 194 differentially expressed genes (DEGs), respectively, that were mainly functionally linked to catalytic activity and binding process. Pull-down experiments showed that ThTrx bound 2-Cys peroxiredoxin BAS1-like protein that influences stress response-associated redox, hormone signal transduction, and transcription factor functions. Therefore, this work provides important insights into ThTrx5 mechanisms that promote salt tolerance in plants.

12.
Carbohydr Polym ; 231: 115714, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888845

RESUMO

Although supramolecular prodrug self-assemblies have been proven as efficient nanocarriers for cancer therapy, tedious synthesis procedures have made their practical applications more difficult. In this paper, ß-cyclodextrin-based supramolecular self-assemblies (SSAs) were directly constructed by utilizing ß-cyclodextrin trimer (ß-CD3) as the host unit and unmodified curcumin as the guest unit. Due to the adjustment of host-guest inclusion and hydrophilic-hydrophobic interactions occurring in the SSAs, their morphology could be readily tuned by changing the ratio of the two components. Different self-assembly morphologies, such as spherical complex micelles, spindle-like complex micelles and multi-compartment vesicles, were obtained. Furthermore, basic cell experiments were performed to study the corresponding effects of the SSA shape on their biological properties. Compared to the other micelles, the spindle-like complex micelles exhibited enhanced cellular toxicity, uptake behaviors and apoptosis rates, and the spherical complex micelles exhibited poor performance. The performance of the multi-compartment vesicles was similar to that of the spindle-like complex micelles. The facile construction of these shape-regulated SSAs and their different cellular biological properties might be valuable in the controlled drug release field.

13.
Chem Commun (Camb) ; 56(12): 1811-1814, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31950951

RESUMO

We developed a label-free homogeneous photoelectrochemical biosensing strategy based on the synergy of G-quadruplex/hemin catalysed electron donor consumption and the inner filter effect for highly selective and sensitive microRNA assay.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Hemina/metabolismo , MicroRNAs/análise , Elétrons , Quadruplex G , Humanos , Processos Fotoquímicos
14.
Biomacromolecules ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31955566

RESUMO

Current therapy for liver failure and concomitant hyperbilirubinemia faces the challenge of poor hemocompatibility and bleeding risks associated with the anticoagulant injection. Herein, heparin-mimetic biomacromolecule (HepMBm) with a similar degree of sulfation and anticoagulant properties to heparin was synthesized by imitating the structure of natural biomacromolecule heparin. Then HepMBm was used to prepare nanocomposite spheres based on reduced graphene oxide (rGO). The formation of a dual-network structure in the spheres endowed the spheres with improved dimensional stability. The proposed spheres exhibited outstanding blood compatibilities and excellent self-anticoagulant properties. The bilirubin adsorption experiments and whole blood bilirubin removal assay indicated that the spheres exhibited high bilirubin removal capability from whole blood (The removal ratio was 99.69%.). The spheres open new routes for a therapeutic strategy without a plasma separation system and heparin pump, which may be a step toward a lightweight wearable artificial liver.

15.
Bioorg Chem ; 95: 102927, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931286

RESUMO

Three new methylated Δ8-pregnene steroids, stemphylisteroids A-C (1-3) were isolated from the medicinal plant Polyalthia laui-derived fungus Stemphylium sp. AZGP4-2. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. The absolute configuration of 1 was determined by X-ray crystallographic analysis. Compound 1 show antibacterial activity against Escherichia coli with the MIC value of 6.25 µg/mL, and 2 exhibited a broad spectrum of antibacterial activities against six pathogenic bacteria with the MIC values ranging from 12.5 to 50 µg/mL. The discovery of three methylated Δ8-pregnene steroids 1-3 are a further addition to diverse and complex array of methylated steroids.

16.
Anticancer Drugs ; 31(4): 411-422, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31929350

RESUMO

The aim of this study was to probe the influence of microRNA-301b (miR-301b) in esophageal cancer pathogenesis. Based on the data acquired from The Cancer Genome Atlas database, we found that miR-301b was highly expressed in esophageal cancer tissues and high expression of miR-301b was related to worse prognosis in patients with esophageal cancer. Quantitative real-time PCR revealed that the expression of miR-301b was higher in all examined esophageal cancer cell lines (ECA109, KY-SE150, TE-1, and NEC) than that in a human esophageal epithelial cell line (HEEC). Upregulation/downregulation of miR-301b facilitated/suppressed the growth, migration, and invasion of ECA109/KY-SE150 cells. Synaptosome-associated protein 91 (SNAP91) was proved to be one of the target genes of miR-301b and was negatively modulated by miR-301b. Besides, SNAP91 was lowly expressed in human esophageal cancer tissues and cell lines. Meanwhile, low expression of SNAP91 was concerned with poor prognosis in patients with esophageal cancer. Furthermore, we discovered that overexpression/depletion of SNAP91 suppressed/facilitated the proliferation of KY-SE150/ECA109 cells. MiR-301b and SNAP91 had little impact on HEEC cell proliferation and this degree of influence was negligible compared with their impacts on esophageal cancer cell proliferation. By rescue assay, we showed that overexpression of SNAP91 restrained the growth, migration, and invasion of ECA109 cells with overexpressed miR-301b while knockdown of SNAP91 showed the contrary effects on KY-SE150 cells with downregulated miR-301b. These consequences indicated that miR-301b played an important effect on esophageal cancer cells through regulating SNAP91, insinuating that miR-301b/SNAP91 might be novel potential targets for esophageal cancer therapy and prognosis.

17.
Int J Biol Macromol ; 145: 876-884, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31765753

RESUMO

Insects can exhibit flexible olfaction that is sensitive to complex natural chemical environments. Odorant-binding proteins (OBPs) in insects' antennal chemosensilla can act as transporters of plant volatiles and pheromones across the sensillar lymph. Although the physiological functions of OBPs have been widely reported, it is still unclear how OBP binds to ligands with various structures in detail. Here, we further investigated the ligand-binding modes and characteristics of AcerOBP2 from the Eastern honey bee (Apis cerana). The results showed that, as a specific protein distributed below the base of chemosensilla on the antennal surface, AcerOBP2 was strongly bound with the candidate floral volatiles and bee pheromones. By docking analysis and site-directed mutagenesis, four different binding modes were found in the five AcerOBP2 mutants between six ligands. Two key amino acids, Ser123 and Lys51, play a key role in AcerOBP2 binding to odors, depending on the presence or absence of hydrogen bonds. In addition, the binding modes depend on their chemical structures and the binding poses of the diverse ligands. These results not only further prompted the functional basis of the relationship between the chemical structures of odorants and bee OBPs, but also revealed the complexity of the flexible behavioral modes of odor binding in insect olfactory systems.

18.
New Phytol ; 225(3): 1193-1205, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31545519

RESUMO

Variation in temperature (T) is usually accompanied by changes in leaf water potential (Ψleaf ), which may influence mesophyll conductance (gm ). However, the effects of Ψleaf on gm have not yet been considered in models of the gm response to temperature. Temperature responses of gm and Ψleaf and the response of gm to Ψleaf were studied in rice (Oryza sativa) and wheat (Triticum aestivum), and then an empirical model of Ψleaf was incorporated into an existing gm -T model. In wheat, Ψleaf was dramatically decreased with increasing T, whereas in rice Ψleaf was less sensitive or insensitive to T. Without taking Ψleaf into account, gm for wheat showed no response to T. However, at a given Ψleaf , gm was significantly higher at high temperature compared with low. After incorporating the function of Ψleaf into the gm -T model, we suggest that the gm -T relationship can be influenced by the activation and deactivation energy for membrane permeability, Ψleaf gradient between temperatures, and the sensitivity of gm to Ψleaf , below a threshold (Ψleaf,0 ). The data presented here suggest that Ψleaf plays an important role in the gm -T relationship and should be considered in future studies related to the temperature response of gm and photosynthesis.

19.
Int J Cancer ; 146(4): 1042-1051, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31396961

RESUMO

Esophageal squamous cell carcinoma (ESCC) occurs with highest frequency in China with over 90% mortality, highlighting the need for early detection and improved treatment strategies. We aimed to identify ESCC cancer predisposition gene(s). Our study included 4,517 individuals. The discovery phase using whole-exome sequencing (WES) included 186 familial ESCC patients from high-risk China. Targeted gene sequencing validation of 598 genes included 3,289 Henan and 1,228 moderate-risk Hong Kong Chinese. A WES approach identified BRCA2 loss-of-function (LOF) mutations in 3.23% (6/186) familial ESCC patients compared to 0.21% (9/4300) in the ExAC East Asians (odds ratio [OR] = 15.89, p = 2.48 × 10-10 ). BRCA2 LOF mutation frequency in the combined Henan cohort has significantly higher prevalence (OR = 10.55, p = 0.0035). Results were independently validated in an ESCC Hong Kong cohort (OR = 10.64, p = 0.022). One Hong Kong pedigree was identified to carry a BRCA2 LOF mutation. BRCA2 inactivation in ESCC was via germline LOF mutations and wild-type somatic allelic loss via loss of heterozygosity. Gene-based association analysis, including LOF mutations and rare deleterious missense variants defined with combined annotation dependent depletion score ≥30, confirmed the genetic predisposition role of BRCA2 (OR = 9.50, p = 3.44 × 10-5 ), and provided new evidence for potential association of ESCC risk with DNA repair genes (POLQ and MSH2), inflammation (TTC39B) and angiogenesis (KDR). Our findings are the first to provide compelling evidence of the role of BRCA2 in ESCC genetic susceptibility in Chinese, suggesting defective homologous recombination is an underlying cause in ESCC pathogenesis, which is amenable to therapeutic options based on synthetic lethality approaches such as targeting BRCA2 with PARP1 inhibitors in ESCC.


Assuntos
Proteína BRCA2/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Genes BRCA2 , Mutação em Linhagem Germinativa , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , China , Estudos de Coortes , Exoma , Feminino , Predisposição Genética para Doença , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Penetrância
20.
Cell Death Differ ; 27(3): 1052-1066, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31358914

RESUMO

The initiation and transduction of DNA damage response (DDR) occur in the context of chromatin, and modifications as well as the structure of chromatin are crucial for DDR signaling. How the profound chromatin alterations are confined to DNA lesions by epigenetic factors remains largely unclear. Here, we discover that JMJD6, a Jumonji C domain-containing protein, is recruited to DNA double-strand breaks (DSBs) after microirradiation. JMJD6 controls the spreading of histone ubiquitination, as well as the subsequent accumulation of repair proteins and transcriptional silencing around DSBs, but does not regulate the initial DNA damage sensing. Furthermore, JMJD6 deficiency results in promotion of the efficiency of nonhomologous end joining (NHEJ) and homologous recombination (HR), rapid cell-cycle checkpoint recovery, and enhanced survival after irradiation. Regarding the mechanism involved, we demonstrate that JMJD6, independently of its catalytic activity, interacts with SIRT1 and recruits it to chromatin to downregulate H4K16ac around DSBs. Our study reveals JMJD6 as a modulator of the epigenome around DNA lesions, and adds to the understanding of the role of epigenetic factors in DNA damage response.

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