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DNA and RNA Modifications in Epigenetic Regulation and Disease
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DNA and RNA Modifications in Epigenetic Regulation and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 16183

Special Issue Editors

Dr. Daniel Gackowski

E-Mail Website
Guest Editor
Department of Clinical Biochemistry, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland
Interests: DNA; RNA; cancer biology; chromatography; cell biology; antioxidants; reactive oxygen species; mutation; oxidative stress; tandem mass spectrometry; biomarkers; medicinal chemistry; vitamins; targeted metabolomics
Dr. Alexey Ruzov

E-Mail Website
Guest Editor
Department of Stem Cell Biology, University of Nottingham, Nottingham, UK
Interests: DNA and RNA modifications; epigenetics; epitranscriptomics; developmental biology; DNA (de)methylation; R-loops; RNA:DNA hybrids; genome stability regulation

Special Issue Information

Dear Colleagues,

The DNA and RNA of all living cells undergoes continuous structural chemical alterations occurring due to exposure to exogenous sources, or generated via endogenous metabolic pathways. Thus, it has been estimated that approximately 70,000 DNA lesions are generated every day in a single cell. Some of these modifications have been linked to a wide variety of diseases, including cancer.

Our current knowledge of the levels, genomic distribution and the degree of involvement of metabolic and environmental factors in the generation of RNA/DNA modifications is insufficient. Therefore, novel approaches for reliable identification, quantification and mapping the modifications in the genome and trascriptome can provide an insight into the mechanism of their action and biological relevance. Moreover, these techniques DNA may also be helpful as a clinical parameter for treatment monitoring, risk group identificationm and development of prevention strategies for a number of diseases.

This open access Special Issue will bring together original research and review articles on new findings, methods, and technical advances in molecular biology and functional consequences of nucleic acids modifications, including new methodological approaches and applications of established techniques.

The main feature of this Special Issue is to provide an open-source sharing of significant works that can increase our understanding of functional consequences of DNA and RNA modifications.

Dr. Daniel Gackowski
Dr. Alexey Ruzov
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Epigenetics
  • DNA modifications
  • RNA modifications
  • Biomarkers
  • Methylation
  • Oxidative stress
  • 8-oxo-7,8-dihydroguanine
  • 5-hydroxymethylcytosine
  • 5-formylcytosine
  • 5-carboxycytosine
  • 5-hydroxymethyluracil
  • N6-methyladenine
  • Uracil
  • Crosslinks
  • Cancer
  • DNA damage
  • DNA repair
  • Metabolomics

Published Papers (4 papers)

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Research

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15 pages, 2789 KiB  
Article
Kaiso Regulates DNA Methylation Homeostasis
by Darya Kaplun, Alexey Starshin, Fedor Sharko, Kristina Gainova, Galina Filonova, Nadezhda Zhigalova, Alexander Mazur, Egor Prokhortchouk and Svetlana Zhenilo
Int. J. Mol. Sci. 2021, 22(14), 7587; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147587 - 15 Jul 2021
Cited by 12 | Viewed by 3519
Abstract
Gain and loss of DNA methylation in cells is a dynamic process that tends to achieve an equilibrium. Many factors are involved in maintaining the balance between DNA methylation and demethylation. Previously, it was shown that methyl-DNA protein Kaiso may attract NCoR, SMRT [...] Read more.
Gain and loss of DNA methylation in cells is a dynamic process that tends to achieve an equilibrium. Many factors are involved in maintaining the balance between DNA methylation and demethylation. Previously, it was shown that methyl-DNA protein Kaiso may attract NCoR, SMRT repressive complexes affecting histone modifications. On the other hand, the deficiency of Kaiso resulted in reduced methylation of ICR in H19/Igf2 locus and Oct4 promoter in mouse embryonic fibroblasts. However, nothing is known about how Kaiso influences DNA methylation at the genome level. Here we show that deficiency of Kaiso led to whole-genome hypermethylation, using Kaiso deficient human renal cancer cell line obtained via CRISPR/CAS9 genome editing. However, Kaiso serves to protect genic regions, enhancers, and regions with a low level of histone modifications from demethylation. We detected hypomethylation of binding sites for Oct4 and Nanog in Kaiso deficient cells. Kaiso immunoprecipitated with de novo DNA methyltransferases DNMT3a/3b, but not with maintenance methyltransferase DNMT1. Thus, Kaiso may attract methyltransferases to surrounding regions and modulate genome methylation in renal cancer cells apart from being methyl DNA binding protein. Full article
(This article belongs to the Special Issue DNA and RNA Modifications in Epigenetic Regulation and Disease)
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Review

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17 pages, 434 KiB  
Review
Methylation and Noncoding RNAs in Gastric Cancer: Everything Is Connected
by Irina V. Bure and Marina V. Nemtsova
Int. J. Mol. Sci. 2021, 22(11), 5683; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115683 - 26 May 2021
Cited by 15 | Viewed by 3304
Abstract
Despite recent progress, gastric cancer remains one of the most common cancers and has a high mortality rate worldwide. Aberrant DNA methylation pattern and deregulation of noncoding RNA expression appear in the early stages of gastric cancer. Numerous investigations have confirmed their significant [...] Read more.
Despite recent progress, gastric cancer remains one of the most common cancers and has a high mortality rate worldwide. Aberrant DNA methylation pattern and deregulation of noncoding RNA expression appear in the early stages of gastric cancer. Numerous investigations have confirmed their significant role in gastric cancer tumorigenesis and their high potential as diagnostic and prognostic biomarkers. Currently, it is clear that these epigenetic regulators do not work alone but interact with each other, generating a complex network. The aim of our review was to summarize the current knowledge of this interaction in gastric cancer and estimate its clinical potential for the diagnosis, prognosis, and treatment of the disease. Full article
(This article belongs to the Special Issue DNA and RNA Modifications in Epigenetic Regulation and Disease)
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24 pages, 554 KiB  
Review
The Molecular Basis of Alcohol Use Disorder (AUD). Genetics, Epigenetics, and Nutrition in AUD: An Amazing Triangle
by Agnieszka Siomek-Gorecka, Anna Dlugosz and Damian Czarnecki
Int. J. Mol. Sci. 2021, 22(8), 4262; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084262 - 20 Apr 2021
Cited by 13 | Viewed by 4384
Abstract
Alcohol use disorder (AUD) is a very common and complex disease, as alcohol is the most widely used addictive drug in the world. This disorder has an enormous impact on public health and social and private life, and it generates a huge number [...] Read more.
Alcohol use disorder (AUD) is a very common and complex disease, as alcohol is the most widely used addictive drug in the world. This disorder has an enormous impact on public health and social and private life, and it generates a huge number of social costs. Alcohol use stimulates hypothalamic–pituitary–adrenal (HPA) axis responses and is the cause of many physical and social problems (especially liver disease and cancer), accidental injury, and risky sexual behavior. For years, researchers have been trying to identify the genetic basis of alcohol use disorder, the molecular mechanisms responsible for its development, and an effective form of therapy. Genetic and environmental factors are known to contribute to the development of AUD, and the expression of genes is a complicated process that depends on epigenetic modulations. Dietary nutrients, such as vitamins, may serve as one these modulators, as they have a direct impact on epigenomes. In this review, we connect gathered knowledge from three emerging fields—genetics, epigenetics, and nutrition—to form an amazing triangle relating to alcohol use disorder. Full article
(This article belongs to the Special Issue DNA and RNA Modifications in Epigenetic Regulation and Disease)
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17 pages, 8194 KiB  
Review
Genomic Uracil and Aberrant Profile of Demethylation Intermediates in Epigenetics and Hematologic Malignancies
by Ryszard Olinski, Geir Slupphaug, Marek Foksinski and Hans Einar Krokan
Int. J. Mol. Sci. 2021, 22(8), 4212; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084212 - 19 Apr 2021
Cited by 6 | Viewed by 4296
Abstract
DNA of all living cells undergoes continuous structural and chemical alterations resulting from fundamental cellular metabolic processes and reactivity of normal cellular metabolites and constituents. Examples include enzymatically oxidized bases, aberrantly methylated bases, and deaminated bases, the latter largely uracil from deaminated cytosine. [...] Read more.
DNA of all living cells undergoes continuous structural and chemical alterations resulting from fundamental cellular metabolic processes and reactivity of normal cellular metabolites and constituents. Examples include enzymatically oxidized bases, aberrantly methylated bases, and deaminated bases, the latter largely uracil from deaminated cytosine. In addition, the non-canonical DNA base uracil may result from misincorporated dUMP. Furthermore, uracil generated by deamination of cytosine in DNA is not always damage as it is also an intermediate in normal somatic hypermutation (SHM) and class shift recombination (CSR) at the Ig locus of B-cells in adaptive immunity. Many of the modifications alter base-pairing properties and may thus cause replicative and transcriptional mutagenesis. The best known and most studied epigenetic mark in DNA is 5-methylcytosine (5mC), generated by a methyltransferase that uses SAM as methyl donor, usually in CpG contexts. Oxidation products of 5mC are now thought to be intermediates in active demethylation as well as epigenetic marks in their own rights. The aim of this review is to describe the endogenous processes that surround the generation and removal of the most common types of DNA nucleobase modifications, namely, uracil and certain epigenetic modifications, together with their role in the development of hematological malignances. We also discuss what dictates whether the presence of an altered nucleobase is defined as damage or a natural modification. Full article
(This article belongs to the Special Issue DNA and RNA Modifications in Epigenetic Regulation and Disease)
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