69 results match your criteria chromatin ended

Engineering nucleosomes for generating diverse chromatin assemblies.

Nucleic Acids Res 2021 05;49(9):e52

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore.

Structural characterization of chromatin is challenging due to conformational and compositional heterogeneity in vivo and dynamic properties that limit achievable resolution in vitro. Although the maximum resolution for solving structures of large macromolecular assemblies by electron microscopy has recently undergone profound increases, X-ray crystallographic approaches may still offer advantages for certain systems. One such system is compact chromatin, wherein the crystalline state recapitulates the crowded molecular environment within the nucleus. Read More

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Single-strand DNA breaks cause replisome disassembly.

Mol Cell 2021 03 22;81(6):1309-1318.e6. Epub 2021 Jan 22.

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA. Electronic address:

DNA damage impedes replication fork progression and threatens genome stability. Upon encounter with most DNA adducts, the replicative CMG helicase (CDC45-MCM2-7-GINS) stalls or uncouples from the point of synthesis, yet eventually resumes replication. However, little is known about the effect on replication of single-strand breaks or "nicks," which are abundant in mammalian cells. Read More

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ATRX and RECQ5 define distinct homologous recombination subpathways.

Proc Natl Acad Sci U S A 2021 01;118(3)

Radiation Biology and DNA Repair, Technical University of Darmstadt, 64287 Darmstadt, Germany

Homologous recombination (HR) is an important DNA double-strand break (DSB) repair pathway that copies sequence information lost at the break site from an undamaged homologous template. This involves the formation of a recombination structure that is processed to restore the original sequence but also harbors the potential for crossover (CO) formation between the participating molecules. Synthesis-dependent strand annealing (SDSA) is an HR subpathway that prevents CO formation and is thought to predominate in mammalian cells. Read More

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January 2021

Evidence for anaphase pulling forces during C. elegans meiosis.

J Cell Biol 2020 12;219(12)

Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA.

Anaphase chromosome movement is thought to be mediated by pulling forces generated by end-on attachment of microtubules to the outer face of kinetochores. However, it has been suggested that during C. elegans female meiosis, anaphase is mediated by a kinetochore-independent pushing mechanism with microtubules only attached to the inner face of segregating chromosomes. Read More

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December 2020

Near-atomic resolution structures of interdigitated nucleosome fibres.

Nat Commun 2020 09 21;11(1):4747. Epub 2020 Sep 21.

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.

Chromosome structure at the multi-nucleosomal level has remained ambiguous in spite of its central role in epigenetic regulation and genome dynamics. Recent investigations of chromatin architecture portray diverse modes of interaction within and between nucleosome chains, but how this is realized at the atomic level is unclear. Here we present near-atomic resolution crystal structures of nucleosome fibres that assemble from cohesive-ended dinucleosomes with and without linker histone. Read More

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September 2020

Epigenetics of Drug Addiction.

Cold Spring Harb Perspect Med 2020 Jun 8. Epub 2020 Jun 8.

Department of Neuroscience.

Substance use disorders (SUDs) are chronic brain diseases characterized by transitions from recreational to compulsive drug use and aberrant drug craving that persists for months to years after abstinence is achieved. The transition to compulsive drug use implies that plasticity is occurring, altering the physiology of the brain to precipitate addicted states. Epigenetic phenomena represent a varied orchestra of transcriptional tuning mechanisms that, in response to environmental stimuli, create and maintain gene expression-mediated physiological outcomes. Read More

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After the break: DSB end processing in mouse meiosis.

Genes Dev 2020 06;34(11-12):731-732

Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

The exchange of genetic information between parental chromosomes in meiosis is an integral process for the creation of gametes. To generate a crossover, hundreds of DNA double-strand breaks (DSBs) are introduced in the genome of each meiotic cell by the SPO11 protein. The nucleolytic resection of DSB-adjacent DNA is a key step in meiotic DSB repair, but this process has remained understudied. Read More

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Tight DNA-protein complexes isolated from barley seedlings are rich in potential guanine quadruplex sequences.

PeerJ 2020 18;8:e8569. Epub 2020 Feb 18.

Faculty of Medicine, University of Latvia, Riga, Latvia.

Background: The concept of chromatin domains attached to the nuclear matrix is being revisited, with nucleus described as a set of topologically associating domains. The significance of the tightly bound to DNA proteins (TBP), a protein group that remains attached to DNA after its deproteinization should be also revisited, as the existence of these interactions is in good agreement with the concept of the topologically associating domain. The work aimed to characterize the DNA component of TBP isolated from barley seedlings. Read More

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February 2020

The human HELLS chromatin remodelling protein promotes end resection to facilitate homologous recombination and contributes to DSB repair within heterochromatin.

Nucleic Acids Res 2020 02;48(4):1872-1885

DNA-protein Interactions Unit, School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.

Efficient double-strand break repair in eukaryotes requires manipulation of chromatin structure. ATP-dependent chromatin remodelling enzymes facilitate different DNA repair pathways, during different stages of the cell cycle and in varied chromatin environments. The contribution of remodelling factors to double-strand break repair within heterochromatin during G2 is unclear. Read More

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February 2020

Histone modification in the lung injury and recovery of mice in response to PM exposure.

Chemosphere 2019 Apr 11;220:127-136. Epub 2018 Dec 11.

College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China. Electronic address:

Epidemiological and experimental studies have progressively provided a better knowledge of the underlying mechanisms by which fine particulate matter (PM) exerts its harmful health effects. However, limited studies focused on the effect and following recovery after the particulate exposure ended. In this study, we determined PM exposure-caused effects on the lung and their recovery in mice after terminating aspiration, and clarified the possible molecular modification. Read More

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Rad51 recruitment and exclusion of non-homologous end joining during homologous recombination at a Tus/Ter mammalian replication fork barrier.

PLoS Genet 2018 07 19;14(7):e1007486. Epub 2018 Jul 19.

Department of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.

Classical non-homologous end joining (C-NHEJ) and homologous recombination (HR) compete to repair mammalian chromosomal double strand breaks (DSBs). However, C-NHEJ has no impact on HR induced by DNA nicking enzymes. In this case, the replication fork is thought to convert the DNA nick into a one-ended DSB, which lacks a readily available partner for C-NHEJ. Read More

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HIF-dependent and reversible nucleosome disassembly in hypoxia-inducible gene promoters.

Exp Cell Res 2018 05 21;366(2):181-191. Epub 2018 Mar 21.

Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Republic of Singapore.

Hypoxia causes dramatic changes in gene expression profiles, and the mechanism of hypoxia-inducible transcription has been analyzed for use as a model system of stress-inducible gene regulation. In this study, changes in chromatin organization in promoters of hypoxia-inducible genes were investigated during hypoxia-reoxygenation conditions. Most of the hypoxia-inducible gene promoters were hypersensitive to DNase I under both normal and hypoxic conditions, and our data indicate an immediate recruitment of transcription factors under hypoxic conditions. Read More

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Genome-wide mapping of global-to-local genetic effects on human facial shape.

Nat Genet 2018 03 19;50(3):414-423. Epub 2018 Feb 19.

Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA.

Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample (n = 1,719). Read More

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Genomic origin and nuclear localization of TERRA telomeric repeat-containing RNA: from Darkness to Dawn.

FEBS J 2018 04 29;285(8):1389-1398. Epub 2017 Dec 29.

Genetic & Epigenetic Alterations of Genomes, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.

Long noncoding RNAs, produced from distinct regions of the chromosomes, are emerging as new key players in several important biological processes. The long noncoding RNAs add a new layer of complexity to cellular regulatory pathways, from transcription to cellular trafficking or chromatin remodeling. More than 25 years ago, the discovery of a transcriptional activity at telomeres of protozoa ended the long-lasting belief that telomeres were transcriptionally silent. Read More

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CIPHER: a flexible and extensive workflow platform for integrative next-generation sequencing data analysis and genomic regulatory element prediction.

BMC Bioinformatics 2017 Aug 8;18(1):363. Epub 2017 Aug 8.

Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Background: Next-generation sequencing (NGS) approaches are commonly used to identify key regulatory networks that drive transcriptional programs. Although these technologies are frequently used in biological studies, NGS data analysis remains a challenging, time-consuming, and often irreproducible process. Therefore, there is a need for a comprehensive and flexible workflow platform that can accelerate data processing and analysis so more time can be spent on functional studies. Read More

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Regulation of repair pathway choice at two-ended DNA double-strand breaks.

Atsushi Shibata

Mutat Res 2017 10 29;803-805:51-55. Epub 2017 Jul 29.

Education and Research Support Center, Gunma University and Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. Electronic address:

A DNA double-strand break (DSB) is considered to be a critical DNA lesion because its misrepair can cause severe mutations, such as deletions or chromosomal translocations. For the precise repair of DSBs, the repair pathway that is optimal for the particular circumstance needs to be selected. Non-homologous end joining (NHEJ) functions in G/S/G phase, while homologous recombination (HR) becomes active only in S/G phase after DNA replication. Read More

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October 2017

Protection of Arabidopsis Blunt-Ended Telomeres Is Mediated by a Physical Association with the Ku Heterodimer.

Plant Cell 2017 Jun 5;29(6):1533-1545. Epub 2017 Jun 5.

Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic

Telomeres form specialized chromatin that protects natural chromosome termini from being recognized as DNA double-strand breaks. Plants possess unusual blunt-ended telomeres that are unable to form t-loops or complex with single-strand DNA binding proteins, raising the question of the mechanism behind their protection. We have previously suggested that blunt-ended telomeres in are protected by Ku, a DNA repair factor with a high affinity for DNA ends. Read More

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KRAB zinc-finger proteins contribute to the evolution of gene regulatory networks.

Nature 2017 03 8;543(7646):550-554. Epub 2017 Mar 8.

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

The human genome encodes some 350 Krüppel-associated box (KRAB) domain-containing zinc-finger proteins (KZFPs), the products of a rapidly evolving gene family that has been traced back to early tetrapods. The function of most KZFPs is unknown, but a few have been demonstrated to repress transposable elements in embryonic stem (ES) cells by recruiting the transcriptional regulator TRIM28 and associated mediators of histone H3 Lys9 trimethylation (H3K9me3)-dependent heterochromatin formation and DNA methylation. Depletion of TRIM28 in human or mouse ES cells triggers the upregulation of a broad range of transposable elements, and recent data based on a few specific examples have pointed to an arms race between hosts and transposable elements as an important driver of KZFP gene selection. Read More

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LncRNA Pulldown Combined with Mass Spectrometry to Identify the Novel LncRNA-Associated Proteins.

Methods Mol Biol 2016 ;1402:1-9

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Long noncoding RNAs (LncRNAs) are nonprotein-coding transcripts longer than 200 nucleotides in length. The recent studies have revealed that at least nearly 80 % transcripts in human cells are lncRNA species. Based on their genomic location, most lncRNAs can be characterized as large intergenic noncoding RNAs, natural antisense transcripts, pseudogenes, long intronic ncRNAs, as well as other divergent transcripts. Read More

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October 2016

A new Xist allele driven by a constitutively active promoter is dominated by Xist locus environment and exhibits the parent-of-origin effects.

Development 2015 Dec 28;142(24):4299-308. Epub 2015 Oct 28.

Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu-University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Department of Advanced Bioscience, Graduate School of Agriculture, Kinki University, 3327-204, Nakamachi, Nara 631-8505, Japan

The dosage difference of X-linked genes between the sexes in mammals is compensated for by genetic inactivation of one of the X chromosomes in XX females. A noncoding RNA transcribed from the Xist gene at the onset of X chromosome inactivation coats the X chromosome in cis and induces chromosome-wide heterochromatinization. Here, we report a new Xist allele (Xist(CAG)) driven by a CAG promoter, which is known to be constitutively active in many types of cells. Read More

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December 2015

Nbs1 ChIP-Seq Identifies Off-Target DNA Double-Strand Breaks Induced by AID in Activated Splenic B Cells.

PLoS Genet 2015 Aug 11;11(8):e1005438. Epub 2015 Aug 11.

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.

Activation-induced cytidine deaminase (AID) is required for initiation of Ig class switch recombination (CSR) and somatic hypermutation (SHM) of antibody genes during immune responses. AID has also been shown to induce chromosomal translocations, mutations, and DNA double-strand breaks (DSBs) involving non-Ig genes in activated B cells. To determine what makes a DNA site a target for AID-induced DSBs, we identify off-target DSBs induced by AID by performing chromatin immunoprecipitation (ChIP) for Nbs1, a protein that binds DSBs, followed by deep sequencing (ChIP-Seq). Read More

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PSMC5, a 19S Proteasomal ATPase, Regulates Cocaine Action in the Nucleus Accumbens.

PLoS One 2015 11;10(5):e0126710. Epub 2015 May 11.

Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.

ΔFosB is a stable transcription factor which accumulates in the nucleus accumbens (NAc), a key part of the brain's reward circuitry, in response to chronic exposure to cocaine or other drugs of abuse. While ΔFosB is known to heterodimerize with a Jun family member to form an active transcription factor complex, there has not to date been an open-ended exploration of other possible binding partners for ΔFosB in the brain. Here, by use of yeast two-hybrid assays, we identify PSMC5-also known as SUG1, an ATPase-containing subunit of the 19S proteasomal complex-as a novel interacting protein with ΔFosB. Read More

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February 2016

Hyper-Acetylation of Histone H3K56 Limits Break-Induced Replication by Inhibiting Extensive Repair Synthesis.

PLoS Genet 2015 Feb 23;11(2):e1004990. Epub 2015 Feb 23.

Program of Radiation Biology, Department of Radiation Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Department of Molecular Medicine, Institute of Biotechnology, Universsity of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.

Break-induced replication (BIR) has been implicated in restoring eroded telomeres and collapsed replication forks via single-ended invasion and extensive DNA synthesis on the recipient chromosome. Unlike other recombination subtypes, DNA synthesis in BIR likely relies heavily on mechanisms enabling efficient fork progression such as chromatin modification. Herein we report that deletion of HST3 and HST4, two redundant de-acetylases of histone H3 Lysine 56 (H3K56), inhibits BIR, sensitizes checkpoint deficient cells to deoxyribonucleotide triphosphate pool depletion, and elevates translocation-type gross chromosomal rearrangements (GCR). Read More

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February 2015

DNA double-strand breaks by Cr(VI) are targeted to euchromatin and cause ATR-dependent phosphorylation of histone H2AX and its ubiquitination.

Toxicol Sci 2015 Jan 6;143(1):54-63. Epub 2014 Oct 6.

Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island 02912

Hexavalent chromium is a human respiratory carcinogen that undergoes intracellular activation in vivo primarily via reduction with ascorbate. Replication of Cr-adducted DNA triggers mismatch repair that generates toxic DNA double-strand breaks (DSBs) as secondary lesions. Here, we examined the intranuclear distribution of chromate-induced breaks and a central DSB signaling branch targeting histone H2AX. Read More

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January 2015

The importance of the one carbon cycle nutritional support in human male fertility: a preliminary clinical report.

Reprod Biol Endocrinol 2014 Jul 29;12:71. Epub 2014 Jul 29.

Parthenogen, Via F, Pelli 1, Lugano 6900, Switzerland.

Background: Sperm chromatin structure is often impaired; mainly due to oxidative damage. Antioxidant treatments do not consistently produce fertility improvements and, when given at high doses, they might block essential oxidative processes such as chromatin compaction. This study was intended to assess the effect on male sub-fertility of a pure one carbon cycle nutritional support without strong antioxidants. Read More

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pRNA: NoRC-associated RNA of rRNA operons.

RNA Biol 2014 20;11(1):3-9. Epub 2013 Dec 20.

Department for Bioinformatics; Faculty of Mathematics and Computer Science; Friedrich-Schiller-University Jena; Jena, Germany.

Promoter-associated RNAs (pRNAs) are a family of ~90-100 nt-long divergent RNAs overlapping the promoter of the rRNA (rDNA) operon. pRNA transcripts interact with TIP5, a component of the chromatin remodeling complex NoRC, which recruits enzymes for heterochromatin formation and mediates silencing of rRNA genes. Here we present a comprehensive analysis of pRNA homologs, including different versions per species, as result of in silico studies in available metazoan genome assemblies. Read More

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October 2014

DNA DSB repair pathway choice: an orchestrated handover mechanism.

Br J Radiol 2014 Mar;87(1035):20130685

Genome Damage and Stability Centre, University of Sussex, Brighton, UK.

DNA double strand breaks (DSBs) are potential lethal lesions but can also lead to chromosome rearrangements, a step promoting carcinogenesis. DNA non-homologous end-joining (NHEJ) is the major DSB rejoining process and occurs in all cell cycle stages. Homologous recombination (HR) can additionally function to repair irradiation-induced two-ended DSBs in G2 phase. Read More

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Efficient expression and purification of tag-free Epstein-Barr virus EBNA1 protein in Escherichia coli by auto-induction.

Protein Expr Purif 2012 Nov 26;86(1):7-11. Epub 2012 Aug 26.

DNA Replication and Epigenetics Group, Research Unit Gene Vectors, Helmholtz Zentrum München, Germany.

Epstein-Barr nuclear antigen 1 (EBNA1) is the essential Epstein-Barr virus (EBV) protein at the interface between the EBV genome and the host chromatin. It is EBNA1's task to guarantee replication and segregation of the multicopy closed circular viral genome in infected cells. While EBNA1's functions are relatively well understood, little is known about the molecular mechanisms of EBNA1 mediating chromatin tethering and DNA replication. Read More

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November 2012

The role of homologous recombination in radiation-induced double-strand break repair.

Radiother Oncol 2011 Oct 5;101(1):7-12. Epub 2011 Jul 5.

Genome Damage and Stability Centre, University of Sussex, UK.

DNA double-strand breaks (DSBs) represent the most biologically significant lesions induced by ionizing radiation (IR). HR is the predominant pathway for repairing one-ended DSBs arising in S-phase when the replication fork encounters single-stranded breaks or base damages. Here, we discuss recent findings that two-ended DSBs directly induced by X- or γ-rays in late S- or G2-phase are repaired predominantly by NHEJ, with HR only repairing a sub-fraction of such DSBs. Read More

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October 2011

Factors determining DNA double-strand break repair pathway choice in G2 phase.

EMBO J 2011 Mar 11;30(6):1079-92. Epub 2011 Feb 11.

Genome Damage and Stability Centre, University of Sussex, East Sussex, UK.

DNA non-homologous end joining (NHEJ) and homologous recombination (HR) function to repair DNA double-strand breaks (DSBs) in G2 phase with HR preferentially repairing heterochromatin-associated DSBs (HC-DSBs). Here, we examine the regulation of repair pathway usage at two-ended DSBs in G2. We identify the speed of DSB repair as a major component influencing repair pathway usage showing that DNA damage and chromatin complexity are factors influencing DSB repair rate and pathway choice. Read More

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