16,487 results match your criteria dna linking


Endosomal trafficking and DNA damage checkpoint kinases dictate survival to replication stress by regulating amino acid uptake and protein synthesis.

Dev Cell 2021 Sep 8. Epub 2021 Sep 8.

IFOM, The FIRC Institute of Molecular Oncology, Milan 20139, Italy; Oncology and Haemato-Oncology Department, University of Milan, Milan 20122, Italy. Electronic address:

Atg6 mediates autophagy and endosomal trafficking. We investigated how Atg6 influences replication stress. Combining genetic, genomic, metabolomic, and proteomic approaches, we found that the Vps34-Vps15-Atg6-Vps38-phosphatydilinositol-3 phosphate (PtdIns(3)P) axis sensitizes cells to replication stress by favoring the degradation of plasma membrane amino acid (AA) transporters via endosomal trafficking and ESCRT proteins, while the PtdIns(3)P phosphatases Ymr1 and Inp53 promote survival to replication stress by reversing this process. Read More

View Article and Full-Text PDF
September 2021

Curcumin, a potential initiator of apoptosis via direct interactions with Bcl-xL and Bid.

Proteins 2021 Sep 15. Epub 2021 Sep 15.

Department of Biophysics, University of Mumbai, Mumbai, India.

Apoptosis is a naturally occurring process during the growth and development of multicellular organisms and is increasingly active during times of cellular stress such as in response to intracellular DNA damage when removal of the host cell is paramount to prevent cancer. Unfortunately, once formed, cancer cells become impervious to apoptosis, creating a desperate need to identify an approach to induce apoptosis in these cells. An attractive option is to focus efforts on developing and locating compounds which activate apoptosis using natural compounds. Read More

View Article and Full-Text PDF
September 2021

The STAT3-MYC Axis Promotes Survival of Leukemia Stem Cells by Regulating SLC1A5 and Oxidative Phosphorylation.

Blood 2021 Sep 15. Epub 2021 Sep 15.

University of Colorado, Aurora, Colorado, United States.

AML is characterized by the presence of leukemia stem cells (LSCs), and failure to fully eradicate this population contributes to disease persistence/relapse. Prior studies have characterized metabolic vulnerabilities of LSCs, which demonstrate preferential reliance on oxidative phosphorylation (OXPHOS) for energy metabolism and survival. In the present study, using both genetic and pharmacologic strategies in primary human AML specimens, we show that signal transducer and activator of transcription 3 (STAT3) mediates OXPHOS in LSCs. Read More

View Article and Full-Text PDF
September 2021

The Thioesterase as a Regulator of Lipid Metabolism in Type 2 Diabetes Detected in a Multi-Omics Study of Human Liver.

OMICS 2021 Sep 13. Epub 2021 Sep 13.

Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Type 2 diabetes (T2D) is characterized by pathophysiological alterations in lipid metabolism. One strategy to understand the molecular mechanisms behind these abnormalities is to identify -regulatory elements (CREs) located in chromatin-accessible regions of the genome that regulate key genes. In this study we integrated assay for transposase-accessible chromatin followed by sequencing (ATAC-seq) data, widely used to decode chromatin accessibility, with multi-omics data and publicly available CRE databases to identify candidate CREs associated with T2D for further experimental validations. Read More

View Article and Full-Text PDF
September 2021

The critical role of natural history museums in advancing eDNA for biodiversity studies: a case study with Amazonian fishes.

Sci Rep 2021 Sep 13;11(1):18159. Epub 2021 Sep 13.

Natural History Museum and Institute, Chuo-ku, Chiba, 260-8682, Japan.

Ichthyological surveys have traditionally been conducted using whole-specimen, capture-based sampling with varied but conventional fishing gear. Recently, environmental DNA (eDNA) metabarcoding has emerged as a complementary, and possible alternative, approach to whole-specimen methodologies. In the tropics, where much of the diversity remains undescribed, vast reaches continue unexplored, and anthropogenic activities are constant threats; there have been few eDNA attempts for ichthyological inventories. Read More

View Article and Full-Text PDF
September 2021

Identification and Characterization of Alcohol-related Hepatocellular Carcinoma Prognostic Subtypes based on an Integrative N6-methyladenosine methylation Model.

Int J Biol Sci 2021 14;17(13):3554-3572. Epub 2021 Aug 14.

Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.

Alcohol consumption increases the risk of hepatocellular carcinoma (HCC), and associated with a high mortality rate and poor prognosis. N6-methyladenosine (m6A) methylations play key roles in tumorigenesis and progression. However, our current knowledge about m6A in alcohol-related HCC (A-HCC) remains elucidated. Read More

View Article and Full-Text PDF

Sensitive electrochemical biosensor for Uracil-DNA glycosylase detection based on self-linkable hollow Mn/Ni layered doubled hydroxides as oxidase-like nanozyme for cascade signal amplification.

Biosens Bioelectron 2021 Sep 1;194:113607. Epub 2021 Sep 1.

School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong, 250100, China. Electronic address:

Nanozymes have been widely used in biosensors instead of natural enzymes because of low cost, high stability and ease of storage. However, few works use oxidase-like nanozymes to fabricate electrochemical biosensors. Herein, we proposed a sensitive electrochemical biosensor to detect uracil-DNA glycosylase (UDG) based on the hollow Mn/Ni layered doubled hydroxides (h-Mn/Ni LDHs) as oxidase-like nanozyme. Read More

View Article and Full-Text PDF
September 2021

Ehlers-Danlos syndrome kyphoscoliotic type 2 caused by mutations in the FKBP14 gene: an analysis of five cases.

F1000Res 2021 25;10:502. Epub 2021 Jun 25.

Veltischev Research and Clinical Institute for Pediatrics, Pirogov Russian National Research Medical University, Moscow, 125412, Russian Federation.

 This study deals with a rare (orphan) monogenic connective tissue disorder - Ehlers-Danlos syndrome kyphoscoliotic type 2 (EDSKS2). Kyphoscoliotic type 2 Ehlers-Danlos syndrome is an autosomal recessive disorder caused by mutations in the FKBP14 gene (7p14.3), which encodes the FKBP22 protein. Read More

View Article and Full-Text PDF

A rapid method to visualize human mitochondrial DNA replication through rotary shadowing and transmission electron microscopy.

Nucleic Acids Res 2021 Sep 9. Epub 2021 Sep 9.

IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.

We report a rapid experimental procedure based on high-density in vivo psoralen inter-strand DNA cross-linking coupled to spreading of naked purified DNA, positive staining, low-angle rotary shadowing, and transmission electron microscopy (TEM) that allows quick visualization of the dynamic of heavy strand (HS) and light strand (LS) human mitochondrial DNA replication. Replication maps built on linearized mitochondrial genomes and optimized rotary shadowing conditions enable clear visualization of the progression of the mitochondrial DNA synthesis and visualization of replication intermediates carrying long single-strand DNA stretches. One variant of this technique, called denaturing spreading, allowed the inspection of the fine chromatin structure of the mitochondrial genome and was applied to visualize the in vivo three-strand DNA structure of the human mitochondrial D-loop intermediate with unprecedented clarity. Read More

View Article and Full-Text PDF
September 2021

Electrostatic Drivers of GPx4 Interactions with Membrane, Lipids, and DNA.

Biochemistry 2021 Sep 7. Epub 2021 Sep 7.

Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia 23284, United States.

Glutathione peroxidase 4 (GPx4) serves as the only enzyme that protects membranes through the reduction of lipid hydroperoxides, preventing membrane oxidative damage and cell death through ferroptosis. Recently, GPx4 has gained attention as a therapeutic target for cancer through inhibition and as a target for inflammatory diseases through activation. In addition, GPx4 isoforms perform several distinct moonlighting functions including cysteine cross-linking of protamines during sperm cell chromatin remodeling, a function for which molecular and structural details are undefined. Read More

View Article and Full-Text PDF
September 2021

STAT3-mediated upregulation of the AIM2 DNA sensor links innate immunity with cell migration to promote epithelial tumourigenesis.

Gut 2021 Sep 6. Epub 2021 Sep 6.

Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia

Objective: The absent in melanoma 2 (AIM2) cytosolic pattern recognition receptor and DNA sensor promotes the pathogenesis of autoimmune and chronic inflammatory diseases via caspase-1-containing inflammasome complexes. However, the role of AIM2 in cancer is ill-defined.

Design: The expression of AIM2 and its clinical significance was assessed in human gastric cancer (GC) patient cohorts. Read More

View Article and Full-Text PDF
September 2021

Developmental programming of DNA methylation and gene expression patterns is associated with extreme cardiovascular tolerance to anoxia in the common snapping turtle.

Epigenetics Chromatin 2021 Sep 6;14(1):42. Epub 2021 Sep 6.

Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester, M13 9NT, UK.

Background: Environmental fluctuation during embryonic and fetal development can permanently alter an organism's morphology, physiology, and behaviour. This phenomenon, known as developmental plasticity, is particularly relevant to reptiles that develop in subterranean nests with variable oxygen tensions. Previous work has shown hypoxia permanently alters the cardiovascular system of snapping turtles and may improve cardiac anoxia tolerance later in life. Read More

View Article and Full-Text PDF
September 2021

Structure and dynamics of the chromatin remodeler ALC1 bound to a PARylated nucleosome.

Elife 2021 Sep 6;10. Epub 2021 Sep 6.

Uppsala University, Uppsala, Sweden.

The chromatin remodeler ALC1 is recruited to and activated by DNA damage-induced poly(ADP-ribose) (PAR) chains deposited by PARP1/PARP2/HPF1 upon detection of DNA lesions. ALC1 has emerged as a candidate drug target for cancer therapy as its loss confers synthetic lethality in homologous recombination-deficient cells. However, structure-based drug design and molecular analysis of ALC1 have been hindered by the requirement for PARylation and the highly heterogeneous nature of this post-translational modification. Read More

View Article and Full-Text PDF
September 2021

Long-Term Effects of Maternal Low-Protein Diet and Post-weaning High-Fat Feeding on Glucose Metabolism and Hypothalamic POMC Promoter Methylation in Offspring Mice.

Front Nutr 2021 16;8:657848. Epub 2021 Aug 16.

Department of Endocrinology, Peking University First Hospital, Beijing, China.

Substantial evidence indicated that maternal malnutrition could increase the susceptibility to obesity, insulin resistance, and type 2 diabetes in adulthood. It is increasingly apparent that the brain, especially the hypothalamus, plays a critical role in glucose homeostasis. However, little information is known about the mechanisms linking maternal protein restriction combined with post-weaning high-fat (HF) feeding with altered expression of brain neurotransmitters, and investigations into the epigenetic modifications of hypothalamus in offspring have not been fully elucidated. Read More

View Article and Full-Text PDF

A Hypothesis: Linking Phase Separation to Meiotic Sex Chromosome Inactivation and Sex-Body Formation.

Front Cell Dev Biol 2021 16;9:674203. Epub 2021 Aug 16.

Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL, United States.

During meiotic prophase I, X and Y chromosomes in mammalian spermatocytes only stably pair at a small homologous region called the pseudoautosomal region (PAR). However, the rest of the sex chromosomes remain largely unsynapsed. The extensive asynapsis triggers transcriptional silencing - meiotic sex chromosome inactivation (MSCI). Read More

View Article and Full-Text PDF

DNA methylation changes in African American women with a history of preterm birth from the InterGEN study.

BMC Genom Data 2021 Sep 5;22(1):30. Epub 2021 Sep 5.

Center for Research on People of Color, School of Nursing, Columbia University, 560 W 168th St, Room 605, New York, NY, 10032, USA.

Background: Preterm birth (< 37 weeks' gestation) is a common outcome of pregnancy that has been associated with increased risk of cardiovascular disease for women later in life. Little is known about the physiologic mechanisms underlying this risk. To date, no studies have evaluated if differences in DNA methylation (DNAm) among women who experience preterm birth are short-term or if they persist and are associated with subsequent cardiovascular sequelae or other health disorders. Read More

View Article and Full-Text PDF
September 2021

Transcription factor binding kinetics and transcriptional bursting: What do we really know?

Curr Opin Struct Biol 2021 Sep 1;71:239-248. Epub 2021 Sep 1.

Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy. Electronic address:

In eukaryotes, transcription is a discontinuous process with mRNA being generated in bursts, after the binding of transcription factors (TFs) to regulatory elements on the genome. Live-cell single-molecule microscopy has highlighted that transcriptional bursting can be controlled by tuning TF/DNA binding kinetics. Yet the timescales of these two processes seem disconnected with TF/DNA interactions typically lasting orders of magnitude shorter than transcriptional bursts. Read More

View Article and Full-Text PDF
September 2021

Projecting Ancient Ancestry in Modern-Day Arabians and Iranians: A Key Role of the Past Exposed Arabo-Persian Gulf on Human Migrations.

Genome Biol Evol 2021 Sep;13(9)

i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.

The Arabian Peninsula is strategic for investigations centered on the early structuring of modern humans in the wake of the out-of-Africa migration. Despite its poor climatic conditions for the recovery of ancient human DNA evidence, the availability of both genomic data from neighboring ancient specimens and informative statistical tools allow modeling the ancestry of local modern populations. We applied this approach to a data set of 741,000 variants screened in 291 Arabians and 78 Iranians, and obtained insightful evidence. Read More

View Article and Full-Text PDF
September 2021

Elucidating the Motif for CpG Oligonucleotide Binding to the Dendritic Cell Receptor DEC-205 Leads to Improved Adjuvants for Liver-Resident Memory.

J Immunol 2021 Sep 3. Epub 2021 Sep 3.

Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia;

DEC-205 is a cell-surface receptor that transports bound ligands into the endocytic pathway for degradation or release within lysosomal endosomes. This receptor has been reported to bind a number of ligands, including keratin, and some classes of CpG oligodeoxynucleotides (ODN). In this study, we explore in detail the requirements for binding ODNs, revealing that DEC-205 efficiently binds single-stranded, phosphorothioated ODN of ≥14 bases, with preference for the DNA base thymidine, but with no requirement for a CpG motif. Read More

View Article and Full-Text PDF
September 2021

High-resolution microbiome analysis enabled by linking of 16S rRNA gene sequences with adjacent genomic contexts.

Microb Genom 2021 Sep;7(9)

Thermo Fisher Scientific Baltics, V. A. Graičiūno str. 8, Vilnius 02241, Lithuania.

Sequence-based characterization of bacterial communities has long been a hostage of limitations of both 16S rRNA gene and whole metagenome sequencing. Neither approach is universally applicable, and the main efforts to resolve constraints have been devoted to improvement of computational prediction tools. Here, we present semi-targeted 16S rRNA sequencing (st16S-seq), a method designed for sequencing V1-V2 regions of the 16S rRNA gene along with the genomic locus upstream of the gene. Read More

View Article and Full-Text PDF
September 2021

Effective Medium Model Applied to Biopolymer Solutions.

Appl Spectrosc 2021 Sep 1:37028211042027. Epub 2021 Sep 1.

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia.

Studying dielectric properties of heterogeneous systems is challenged by a problem of uncertainty of the ratio between dielectric permittivity of the system and dielectric permittivities of its components. Such ratios can be obtained in some cases using theoretical effective medium models. However, such models have not yet been developed for all the systems possible. Read More

View Article and Full-Text PDF
September 2021

Immunomodulation-A Molecular Solution to Treating Patients with Severe Bladder Pain Syndrome?

Eur Urol Open Sci 2021 Sep 6;31:49-58. Epub 2021 Aug 6.

Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden.

Background: Patients with bladder pain syndrome experience debilitating pain and extreme frequency of urination. Numerous therapeutic approaches have been tested, but as the molecular basis of disease has remained unclear, specific therapies are not available.

Objective: Recently, a systematic gene deletion strategy identified interleukin-1 (IL-1) hyperactivation as a cause of severe cystitis in a murine model. Read More

View Article and Full-Text PDF
September 2021

Genome-wide mapping of genomic DNA damage: methods and implications.

Cell Mol Life Sci 2021 Aug 31. Epub 2021 Aug 31.

Oxidative Stress Group, Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, 4202 East Fowler Avenue, ISA 6207, Tampa, 33620, USA.

Exposures from the external and internal environments lead to the modification of genomic DNA, which is implicated in the cause of numerous diseases, including cancer, cardiovascular, pulmonary and neurodegenerative diseases, together with ageing. However, the precise mechanism(s) linking the presence of damage, to impact upon cellular function and pathogenesis, is far from clear. Genomic location of specific forms of damage is likely to be highly informative in understanding this process, as the impact of downstream events (e. Read More

View Article and Full-Text PDF

Discovery of Oral Anticancer 1,2-Bis(hydroxymethyl)benzo[]pyrrolo[2,1-]phthalazine Hybrids That Inhibit Angiogenesis and Induce DNA Cross-Links.

J Med Chem 2021 Sep 30;64(17):12469-12486. Epub 2021 Aug 30.

Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.

Designing hybrid molecules with dual functions is one approach to improve the therapeutic efficacy of combination treatment. We have previously conjugated phthalazine and bis(hydroxymethyl)pyrrole pharmacophores to form hybrids bearing antiangiogenesis and DNA interstrand cross-linking activities. To improve the bioavailability, we adopted a benzology approach to design and synthesize a new series of 1,2-bis(hydroxymethyl)benzo[]pyrrolo[2,1-]phthalazines. Read More

View Article and Full-Text PDF
September 2021

Nuclear envelope mechanobiology: linking the nuclear structure and function.

Nucleus 2021 Dec;12(1):90-114

Mechanical and Biomedical Engineering, Boise State University, Boise, ID, US.

The nucleus, central to cellular activity, relies on both direct mechanical input as well as its molecular transducers to sense external stimuli and respond by regulating intra-nuclear chromatin organization that determines cell function and fate. In mesenchymal stem cells of musculoskeletal tissues, changes in nuclear structures are emerging as a key modulator of their differentiation and proliferation programs. In this review we will first introduce the structural elements of the nucleoskeleton and discuss the current literature on how nuclear structure and signaling are altered in relation to environmental and tissue level mechanical cues. Read More

View Article and Full-Text PDF
December 2021

Linking circular intronic RNA degradation and function in transcription by RNase H1.

Sci China Life Sci 2021 Aug 25. Epub 2021 Aug 25.

School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.

Circular intronic RNAs (ciRNAs) escaping from DBR1 debranching of intron lariats are co-transcriptionally produced from pre-mRNA splicing, but their turnover and mechanism of action have remained elusive. We report that RNase H1 degrades a subgroup of ciRNAs in human cells. Many ciRNAs contain high GC% and tend to form DNA:RNA hybrids (R-loops) for RNase H1 cleavage, a process that appears to promote Pol II transcriptional elongation at ciRNA-producing loci. Read More

View Article and Full-Text PDF

Adsorptive Removal of Heavy Metal Ions, Organic Dyes, and Pharmaceuticals by DNA-Chitosan Hydrogels.

Gels 2021 Aug 6;7(3). Epub 2021 Aug 6.

Graduate School of Environmental Studies, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.

DNA-chitosan (DNA-CS) hydrogel was prepared by in situ complexation between oppositely charged DNA and chitosan polyelectrolytes via electrostatic cross-linking to study its adsorption characteristics. The DNA-chitosan hydrogel matrix contains (i) cationic (NH) and anionic (PO) sites for electrostatic binding with ionic species, (ii) -OH and -NH groups and heteroaromatic DNA nucleobases for chelation of heavy metal ions, and (iii) DNA double-helix for recognition and binding to small organic molecules of various structures and polarities. DNA-CS hydrogels efficiently bind with Hg, Pb, Cd, and Cu metal cations of significant environmental concern. Read More

View Article and Full-Text PDF

Interactome Analysis of KIN (Kin17) Shows New Functions of This Protein.

Curr Issues Mol Biol 2021 Jul 22;43(2):767-781. Epub 2021 Jul 22.

Departamento de Biotecnologia, Genética e Biologia Celular, Universidade Estadual de Maringá, Av. Colombo, 5790, Maringá 87020-900, Brazil.

KIN (Kin17) protein is overexpressed in a number of cancerous cell lines, and is therefore considered a possible cancer biomarker. It is a well-conserved protein across eukaryotes and is ubiquitously expressed in all cell types studied, suggesting an important role in the maintenance of basic cellular function which is yet to be well determined. Early studies on KIN suggested that this nuclear protein plays a role in cellular mechanisms such as DNA replication and/or repair; however, its association with chromatin depends on its methylation state. Read More

View Article and Full-Text PDF

Emerging role of air pollution in chronic kidney disease.

Environ Sci Pollut Res Int 2021 Aug 26. Epub 2021 Aug 26.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.

Chronic kidney disease (CKD), a global disease burden related to high rates of incidence and mortality, manifests as progressive and irretrievable nephron loss and decreased kidney regeneration capacity. Emerging studies have suggested that exposure to air pollution is closely relevant to increased risk of CKD, CKD progression and end-stage kidney disease (ESKD). Inhaled airborne particles may cause vascular injury, intraglomerular hypertension, or glomerulosclerosis through non-hemodynamic and hemodynamic factors with multiple complex interactions. Read More

View Article and Full-Text PDF