Biomolecules

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Open AccessFeature PaperReview

Repair of DNA Double-Strand Breaks in Heterochromatin

by Felicity Z. Watts

Biomolecules 2016, 6(4), 47; https://doi.org/10.3390/biom6040047 - 16 Dec 2016

Cited by 21 | Viewed by 9272

DNA double-strand breaks (DSBs) are among the most damaging lesions in DNA, since, if not identified and repaired, they can lead to insertions, deletions or chromosomal rearrangements. DSBs can be in the form of simple or complex breaks, and may be repaired by [...] Read more.

DNA double-strand breaks (DSBs) are among the most damaging lesions in DNA, since, if not identified and repaired, they can lead to insertions, deletions or chromosomal rearrangements. DSBs can be in the form of simple or complex breaks, and may be repaired by one of a number of processes, the nature of which depends on the complexity of the break or the position of the break within the chromatin. In eukaryotic cells, nuclear DNA is maintained as either euchromatin (EC) which is loosely packed, or in a denser form, much of which is heterochromatin (HC). Due to the less accessible nature of the DNA in HC as compared to that in EC, repair of damage in HC is not as straightforward as repair in EC. Here we review the literature on how cells deal with DSBs in HC. Full article

(This article belongs to the Special Issue Chromosome Maintenance)

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Open AccessReview

Epigenetic Impact on EBV Associated B-Cell Lymphomagenesis

by Shatadru Ghosh Roy, Erle S. Robertson and Abhik Saha

Biomolecules 2016, 6(4), 46; https://doi.org/10.3390/biom6040046 - 24 Nov 2016

Cited by 12 | Viewed by 7136

Abstract

Epigenetic modifications leading to either transcriptional repression or activation, play an indispensable role in the development of human cancers. Epidemiological study revealed that approximately 20% of all human cancers are associated with tumor viruses. Epstein-Barr virus (EBV), the first human tumor virus, demonstrates [...] Read more.

Epigenetic modifications leading to either transcriptional repression or activation, play an indispensable role in the development of human cancers. Epidemiological study revealed that approximately 20% of all human cancers are associated with tumor viruses. Epstein-Barr virus (EBV), the first human tumor virus, demonstrates frequent epigenetic alterations on both viral and host genomes in associated cancers—both of epithelial and lymphoid origin. The cell type-dependent different EBV latent gene expression patterns appear to be determined by the cellular epigenetic machinery and similarly viral oncoproteins recruit epigenetic regulators in order to deregulate the cellular gene expression profile resulting in several human cancers. This review elucidates the epigenetic consequences of EBV–host interactions during development of multiple EBV-induced B-cell lymphomas, which may lead to the discovery of novel therapeutic interventions against EBV-associated B-cell lymphomas by alteration of reversible patho-epigenetic markings. Full article

(This article belongs to the Special Issue DNA Methylation and Cancer)

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Open AccessReview

The Emergence of Pan-Cancer CIMP and Its Elusive Interpretation

by Brendan F. Miller, Francisco Sánchez-Vega and Laura Elnitski

Biomolecules 2016, 6(4), 45; https://doi.org/10.3390/biom6040045 - 22 Nov 2016

Cited by 25 | Viewed by 7817

Abstract

Epigenetic dysregulation is recognized as a hallmark of cancer. In the last 16 years, a CpG island methylator phenotype (CIMP) has been documented in tumors originating from different tissues. However, a looming question in the field is whether or not CIMP is a [...] Read more.

Epigenetic dysregulation is recognized as a hallmark of cancer. In the last 16 years, a CpG island methylator phenotype (CIMP) has been documented in tumors originating from different tissues. However, a looming question in the field is whether or not CIMP is a pan-cancer phenomenon or a tissue-specific event. Here, we give a synopsis of the history of CIMP and describe the pattern of DNA methylation that defines the CIMP phenotype in different cancer types. We highlight new conceptual approaches of classifying tumors based on CIMP in a cancer type-agnostic way that reveal the presence of distinct CIMP tumors in a multitude of The Cancer Genome Atlas (TCGA) datasets, suggesting that this phenotype may transcend tissue-type specificity. Lastly, we show evidence supporting the clinical relevance of CIMP-positive tumors and suggest that a common CIMP etiology may define new mechanistic targets in cancer treatment. Full article

(This article belongs to the Special Issue DNA Methylation and Cancer)

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Open AccessReview

The Role of miRNAs in Common Inflammatory Arthropathies: Osteoarthritis and Gouty Arthritis

by Panagiota Papanagnou, Theodora Stivarou and Maria Tsironi

Biomolecules 2016, 6(4), 44; https://doi.org/10.3390/biom6040044 - 11 Nov 2016

Cited by 19 | Viewed by 7967

Abstract

MicroRNAs (miRNAs) are small, non-coding RNA species that are highly evolutionarily conserved, from higher invertebrates to man. Up to 1000 miRNAs have been identified in human cells thus far, where they are key regulators of the expression of numerous targets at the post-transcriptional [...] Read more.

MicroRNAs (miRNAs) are small, non-coding RNA species that are highly evolutionarily conserved, from higher invertebrates to man. Up to 1000 miRNAs have been identified in human cells thus far, where they are key regulators of the expression of numerous targets at the post-transcriptional level. They are implicated in various processes, including cell differentiation, metabolism, and inflammation. An expanding list of miRNAs is known to be involved in the pathogenesis of common, non-autoimmune inflammatory diseases. Interestingly, osteoarthritis (OA) is now being conceptualized as a metabolic disease, as there is a correlation among hyperuricemia and metabolic syndrome (MetS). Experimental evidence suggests that metabolic deregulation is a commonality between these different pathological entities, and that miRNAs are key players in the modulation of metabolic routes. In light of these findings, this review discusses the role of miRNAs in OA and gouty arthritis, as well as the possible therapeutic targetability of miRNAs in these diseases. Full article

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Open AccessArticle

CoverageAnalyzer (CAn): A Tool for Inspection of Modification Signatures in RNA Sequencing Profiles

by Ralf Hauenschild, Stephan Werner, Lyudmil Tserovski, Andreas Hildebrandt, Yuri Motorin and Mark Helm

Biomolecules 2016, 6(4), 42; https://doi.org/10.3390/biom6040042 - 10 Nov 2016

Cited by 16 | Viewed by 5435

Abstract

Combination of reverse transcription (RT) and deep sequencing has emerged as a powerful instrument for the detection of RNA modifications, a field that has seen a recent surge in activity because of its importance in gene regulation. Recent studies yielded high-resolution RT signatures [...] Read more.

Combination of reverse transcription (RT) and deep sequencing has emerged as a powerful instrument for the detection of RNA modifications, a field that has seen a recent surge in activity because of its importance in gene regulation. Recent studies yielded high-resolution RT signatures of modified ribonucleotides relying on both sequence-dependent mismatch patterns and reverse transcription arrests. Common alignment viewers lack specialized functionality, such as filtering, tailored visualization, image export and differential analysis. Consequently, the community will profit from a platform seamlessly connecting detailed visual inspection of RT signatures and automated screening for modification candidates. CoverageAnalyzer (CAn) was developed in response to the demand for a powerful inspection tool. It is freely available for all three main operating systems. With SAM file format as standard input, CAn is an intuitive and user-friendly tool that is generally applicable to the large community of biomedical users, starting from simple visualization of RNA sequencing (RNA-Seq) data, up to sophisticated modification analysis with significance-based modification candidate calling. Full article

(This article belongs to the Collection RNA Modifications)

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Open AccessArticle

Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

by John K. Maxi, Matt Dean, Jovanny Zabaleta, Krzysztof Reiss, Gregory J. Bagby, Steve Nelson, Peter J. Winsauer, Francesca Peruzzi and Patricia E. Molina

Biomolecules 2016, 6(4), 43; https://doi.org/10.3390/biom6040043 - 9 Nov 2016

Cited by 7 | Viewed by 5365

Abstract

Alcohol use disorders (AUD) exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+) patients. We have shown that chronic binge alcohol (CBA) administration (13–14 g EtOH/kg/wk) prior to and during simian immunodeficiency virus (SIV) infection in rhesus macaques unmasks learning deficits in operant learning [...] Read more.

Alcohol use disorders (AUD) exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+) patients. We have shown that chronic binge alcohol (CBA) administration (13–14 g EtOH/kg/wk) prior to and during simian immunodeficiency virus (SIV) infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2) macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2) macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation) were analyzed to determine differentially expressed genes. MetaCore from Thomson Reuters revealed enrichment of genes involved in inflammation, immune responses, and neurodevelopment. Functional relevance of these alterations was examined in vitro by exposing murine neural progenitor cells (NPCs) to ethanol (EtOH) and HIV trans-activator of transcription (Tat) protein. EtOH impaired NPC differentiation as indicated by decreased βIII tubulin expression. These findings suggest a role for neuroinflammation and neurogenesis in CBA/SIV neuropathogenesis and warrant further investigation of their potential contribution to CBA-mediated neurobehavioral deficits. Full article

(This article belongs to the Special Issue Multi-Organ Alcohol-Related Damage: Mechanisms and Treatment)

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Open AccessArticle

Continuous Reusability using Immobilized HasApf in Chemoenzymatic Deracemization: A New Heterogeneous Enzyme Catalysis

by Hiroyuki Nagaoka

Biomolecules 2016, 6(4), 41; https://doi.org/10.3390/biom6040041 - 25 Oct 2016

Cited by 2 | Viewed by 5925

Abstract

This study found that the calibration curve of heme acquisition system A (HasA, a new reactive active species) immobilized by a porous ceramic particle (ImHApf; immobilized HasA from Pseudomonas fluorescens) can be constructed in the range of 1750–1450 cm⁻¹ using Fourier [...] Read more.

This study found that the calibration curve of heme acquisition system A (HasA, a new reactive active species) immobilized by a porous ceramic particle (ImHApf; immobilized HasA from Pseudomonas fluorescens) can be constructed in the range of 1750–1450 cm⁻¹ using Fourier transform infrared spectroscopy (FTIR) analysis, and evaluated its catalytic efficiency. In the asymmetric oxidation of rac-1-(6-methoxynaphthalen-2-yl)ethanol (rac-1: a naproxen precursor), a product ketone from the (R)-isomer is desymmetrized using NaBH₄ and continuously reused even if treated with an organic solvent in 50 mM glycine–NaOH buffer at 40 °C in the absence of nicotinamide adenine dinucleotide (NAD(P)), leading to >99% enantiomeric excess and >90% chemical yield; the activity was calculated at 0.74 ± 0.03 mU/(mg·min) and the turnover number was determined to be approximately 2 × 10⁶. It was confirmed that the other sec-alcohols such as rac-1-(2-naphthyl)ethanol (rac-2) and m- and p-substituted rac-1-phenyl ethanols (rac-3ab–6ab) using ImHApf can also yield a single stereoisomer from a racemate. Therefore, HasA immobilization can be expected to become an important tool for building an environmentally friendly system that promotes industrial sustainability. Full article

(This article belongs to the Special Issue Advances in Heme Proteins)

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Open AccessCorrection

Correction: Pennisi, R., et al. Hsp90: A New Player in DNA Repair? Biomolecules 2015, 5, 2589–2618

by Rosa Pennisi, Paolo Ascenzi and Alessandra Di Masi

Biomolecules 2016, 6(4), 40; https://doi.org/10.3390/biom6040040 - 18 Oct 2016

Cited by 1 | Viewed by 3495

Abstract

n/a Full article

(This article belongs to the Special Issue DNA Damage Response)

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Open AccessReview

Intra- and Extra-Cellular Events Related to Altered Glycosylation of MUC1 Promote Chronic Inflammation, Tumor Progression, Invasion, and Metastasis

by Sandra Cascio and Olivera J. Finn

Biomolecules 2016, 6(4), 39; https://doi.org/10.3390/biom6040039 - 13 Oct 2016

Cited by 56 | Viewed by 9007

Abstract

Altered glycosylation of mucin 1 (MUC1) on tumor cells compared to normal epithelial cells was previously identified as an important antigenic modification recognized by the immune system in the process of tumor immunosurveillance. This tumor form of MUC1 is considered a viable target [...] Read more.

Altered glycosylation of mucin 1 (MUC1) on tumor cells compared to normal epithelial cells was previously identified as an important antigenic modification recognized by the immune system in the process of tumor immunosurveillance. This tumor form of MUC1 is considered a viable target for cancer immunotherapy. The importance of altered MUC1 glycosylation extends also to its role as a promoter of chronic inflammatory conditions that lead to malignant transformation and cancer progression. We review here what is known about the role of specific cancer-associated glycans on MUC1 in protein-protein interactions and intracellular signaling in cancer cells and in their adhesion to each other and the tumor stroma. The tumor form of MUC1 also creates a different landscape of inflammatory cells in the tumor microenvironment by controlling the recruitment of inflammatory cells, establishing specific interactions with dendritic cells (DCs) and macrophages, and facilitating tumor escape from the immune system. Through multiple types of short glycans simultaneously present in tumors, MUC1 acquires multiple oncogenic properties that control tumor development, progression, and metastasis at different steps of the process of carcinogenesis. Full article

(This article belongs to the Special Issue Cancer and Glycosylation)

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Biomolecules, Volume 6, Issue 4 (December 2016) – 9 articles

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