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DNA Damage and Repair

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 44003

Special Issue Editors

Institut de Ciència Molecular, València, Spain
Interests: quantum chemistry of the excited electronic state; DNA photochemistry; DNA photorepair; chemiexcitation; chemi/bioluminescence
Instituto de Tecnología Química (ITQ), Universitat Politècnica de València, Consejo Superior de Investigaciones Científicas, Valencia, Spain
Interests: DNA photochemistry; DNA photorepair; drug photosensitization, photoprotection; energy transfer processes
Departamento de Química Física, Universidad de Valencia, 46100 Burjassot, Spain
Interests: qm/mm simulations; reaction dynamics; enzymatic catalysis; computational biochemistry; free energy calculations

Special Issue Information

Dear Colleagues,

DNA is a molecule of paramount importance due to its fundamental biological role in carrying and storing genetic information. As such, its stability is key for safeguarding DNA integrity from external stress. This is achieved, inter alia, by means of specific repair mechanisms that ensure an efficient and prompt correction of the DNA defects. Nonetheless, some exogenous or endogenous chemical or physical agents may change this well-functioning scenario, provoking the formation of deleterious lesions that, if left unrepaired, threaten cell integrity.

This Special Issue represents an excellent opportunity for researchers of different areas to share their latest progresses and aims at developing a work in the “frontier of knowledge” with an interdisciplinary approach between chemistry (experimental and theoretical), biology, and medicine. The published original articles or reviews will open new paths toward the understanding of the generation and repair of DNA lesions, thus making it possible to advance knowledge of the processes that are at the origin of tumorigenesis.

Dr. Virginie L. Lhiaubet-Vallet
Dr. Daniel Roca-Sanjuán
Prof. Dr. Iñaki Tuñón
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. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • DNA damage
  • DNA repair
  • Photolyase
  • Oxidative damage
  • Electron transfer
  • Cyclobutane pyrimidine dimers
  • (6-4) photoproducts
  • Chemiexcitation
  • Damaged oligonucleotides structure and dynamics
  • G-quadruplexes
  • Charge transfer states

Published Papers (12 papers)

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Research

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16 pages, 3251 KiB  
Article
FOXO3a Mediates Homologous Recombination Repair (HRR) via Transcriptional Activation of MRE11, BRCA1, BRIP1, and RAD50
by Gozde Inci, Madhuri Shende Warkad, Beom-Goo Kang, Na-Kyung Lee, Hong-Won Suh, Soon Sung Lim, Jaebong Kim, Sung-Chan Kim and Jae-Yong Lee
Molecules 2022, 27(23), 8623; https://doi.org/10.3390/molecules27238623 - 06 Dec 2022
Viewed by 1270
Abstract
To test whether homologous recombination repair (HRR) depends on FOXO3a, a cellular aging model of human dermal fibroblast (HDF) and tet-on flag-h-FOXO3a transgenic mice were studied. HDF cells transfected with over-expression of wt-h-FOXO3a increased the protein levels of MRE11, BRCA1, BRIP1, and RAD50, [...] Read more.
To test whether homologous recombination repair (HRR) depends on FOXO3a, a cellular aging model of human dermal fibroblast (HDF) and tet-on flag-h-FOXO3a transgenic mice were studied. HDF cells transfected with over-expression of wt-h-FOXO3a increased the protein levels of MRE11, BRCA1, BRIP1, and RAD50, while knock-down with siFOXO3a decreased them. The protein levels of MRE11, BRCA1, BRIP1, RAD50, and RAD51 decreased during cellular aging. Chromatin immunoprecipitation (ChIP) assay was performed on FOXO3a binding accessibility to FOXO consensus sites in human MRE11, BRCA1, BRIP1, and RAD50 promoters; the results showed FOXO3a binding decreased during cellular aging. When the tet-on flag-h-FOXO3a mice were administered doxycycline orally, the protein and mRNA levels of flag-h-FOXO3a, MRE11, BRCA1, BRIP1, and RAD50 increased in a doxycycline-dose-dependent manner. In vitro HRR assays were performed by transfection with an HR vector and I-SceI vector. The mRNA levels of the recombined GFP increased after doxycycline treatment in MEF but not in wt-MEF, and increased in young HDF comparing to old HDF, indicating that FOXO3a activates HRR. Overall, these results demonstrate that MRE11, BRCA1, BRIP1, and RAD50 are transcriptional target genes for FOXO3a, and HRR activity is increased via transcriptional activation of MRE11, BRCA1, BRIP1, and RAD50 by FOXO3a. Full article
(This article belongs to the Special Issue DNA Damage and Repair)
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24 pages, 4801 KiB  
Article
Interaction of Thymine DNA Glycosylase with Oxidised 5-Methyl-cytosines in Their Amino- and Imino-Forms
by Senta Volkenandt, Frank Beierlein and Petra Imhof
Molecules 2021, 26(19), 5728; https://doi.org/10.3390/molecules26195728 - 22 Sep 2021
Cited by 1 | Viewed by 1852
Abstract
Thymine DNA Glycosylase (TDG) is an enzyme of the base excision repair mechanism and removes damaged or mispaired bases from DNA via hydrolysis of the glycosidic bond. Specificity is of high importance for such a glycosylase, so as to avoid the damage of [...] Read more.
Thymine DNA Glycosylase (TDG) is an enzyme of the base excision repair mechanism and removes damaged or mispaired bases from DNA via hydrolysis of the glycosidic bond. Specificity is of high importance for such a glycosylase, so as to avoid the damage of intact DNA. Among the substrates reported for TDG are mispaired uracil and thymine but also formyl-cytosine and carboxyl-cytosine. Methyl-cytosine and hydroxylmethyl-cytosine are, in contrast, not processed by the TDG enzyme. We have in this work employed molecular dynamics simulations to explore the conformational dynamics of DNA carrying a formyl-cytosine or carboxyl-cytosine and compared those to DNA with the non-cognate bases methyl-cytosine and hydroxylmethyl-cytosine, as amino and imino tautomers. Whereas for the mispairs a wobble conformation is likely decisive for recognition, all amino tautomers of formyl-cytosine and carboxyl-cytosine exhibit the same Watson–Crick conformation, but all imino tautomers indeed form wobble pairs. The conformational dynamics of the amino tautomers in free DNA do not exhibit differences that could be exploited for recognition, and also complexation to the TDG enzyme does not induce any alteration that would indicate preferable binding to one or the other oxidised methyl-cytosine. The imino tautomers, in contrast, undergo a shift in the equilibrium between a closed and a more open, partially flipped state, towards the more open form upon complexation to the TDG enzyme. This stabilisation of the more open conformation is most pronounced for the non-cognate bases methyl-cytosine and hydroxyl-cytosine and is thus not a likely mode for recognition. Moreover, calculated binding affinities for the different forms indicate the imino forms to be less likely in the complexed DNA. These findings, together with the low probability of imino tautomers in free DNA and the indifference of the complexed amino tautomers, suggest that discrimination of the oxidised methyl-cytosines does not take place in the initial complex formation. Full article
(This article belongs to the Special Issue DNA Damage and Repair)
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11 pages, 1942 KiB  
Article
Molecular Determinant of DIDS Analogs Targeting RAD51 Activity
by Denis Velic, Alexandre Demeyer, Thibaut Peterlini, Houda Benhelli-Mokrani, Monique Mathé-Allainmat, Jean-Yves Masson and Fabrice Fleury
Molecules 2021, 26(18), 5460; https://doi.org/10.3390/molecules26185460 - 08 Sep 2021
Cited by 5 | Viewed by 2153
Abstract
RAD51 is the central protein in DNA repair by homologous recombination (HR), involved in several steps of this process. It is shown that overexpression of the RAD51 protein is correlated with increased survival of cancer cells to cancer treatments. For the past decade, [...] Read more.
RAD51 is the central protein in DNA repair by homologous recombination (HR), involved in several steps of this process. It is shown that overexpression of the RAD51 protein is correlated with increased survival of cancer cells to cancer treatments. For the past decade, RAD51 overexpression-mediated resistance has justified the development of targeted inhibitors. One of the first molecules described to inhibit RAD51 was the 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid (DIDS) molecule. This small molecule is effective in inhibiting different functions of RAD51, however its mode of action and the chemical functions involved in this inhibition have not been identified. In this work, we used several commercial molecules derived from DIDS to characterize the structural determinants involved in modulating the activity of RAD51. By combining biochemical and biophysical approaches, we have shown that DIDS and two analogs were able to inhibit the binding of RAD51 to ssDNA and prevent the formation of D-loop by RAD51. Both isothiocyanate substituents of DIDS appear to be essential in the inhibition of RAD51. These results open the way to the synthesis of new molecules derived from DIDS that should be greater modulators of RAD51 and more efficient for HR inhibition. Full article
(This article belongs to the Special Issue DNA Damage and Repair)
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10 pages, 2440 KiB  
Article
Staring at the Naked Goddess: Unraveling the Structure and Reactivity of Artemis Endonuclease Interacting with a DNA Double Strand
by Cécilia Hognon and Antonio Monari
Molecules 2021, 26(13), 3986; https://doi.org/10.3390/molecules26133986 - 29 Jun 2021
Cited by 4 | Viewed by 2128
Abstract
Artemis is an endonuclease responsible for breaking hairpin DNA strands during immune system adaptation and maturation as well as the processing of potentially toxic DNA lesions. Thus, Artemis may be an important target in the development of anticancer therapy, both for the sensitization [...] Read more.
Artemis is an endonuclease responsible for breaking hairpin DNA strands during immune system adaptation and maturation as well as the processing of potentially toxic DNA lesions. Thus, Artemis may be an important target in the development of anticancer therapy, both for the sensitization of radiotherapy and for immunotherapy. Despite its importance, its structure has been resolved only recently, and important questions concerning the arrangement of its active center, the interaction with the DNA substrate, and the catalytic mechanism remain unanswered. In this contribution, by performing extensive molecular dynamic simulations, both classically and at the hybrid quantum mechanics/molecular mechanics level, we evidenced the stable interaction modes of Artemis with a model DNA strand. We also analyzed the catalytic cycle providing the free energy profile and key transition states for the DNA cleavage reaction. Full article
(This article belongs to the Special Issue DNA Damage and Repair)
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14 pages, 3448 KiB  
Article
Theoretical Study on the Photo-Oxidation and Photoreduction of an Azetidine Derivative as a Model of DNA Repair
by Miriam Navarrete-Miguel, Antonio Francés-Monerris, Miguel A. Miranda, Virginie Lhiaubet-Vallet and Daniel Roca-Sanjuán
Molecules 2021, 26(10), 2911; https://doi.org/10.3390/molecules26102911 - 14 May 2021
Cited by 5 | Viewed by 1812
Abstract
Photocycloreversion plays a central role in the study of the repair of DNA lesions, reverting them into the original pyrimidine nucleobases. Particularly, among the proposed mechanisms for the repair of DNA (6-4) photoproducts by photolyases, it has been suggested that it takes place [...] Read more.
Photocycloreversion plays a central role in the study of the repair of DNA lesions, reverting them into the original pyrimidine nucleobases. Particularly, among the proposed mechanisms for the repair of DNA (6-4) photoproducts by photolyases, it has been suggested that it takes place through an intermediate characterized by a four-membered heterocyclic oxetane or azetidine ring, whose opening requires the reduction of the fused nucleobases. The specific role of this electron transfer step and its impact on the ring opening energetics remain to be understood. These processes are studied herein by means of quantum-chemical calculations on the two azetidine stereoisomers obtained from photocycloaddition between 6-azauracil and cyclohexene. First, we analyze the efficiency of the electron-transfer processes by computing the redox properties of the azetidine isomers as well as those of a series of aromatic photosensitizers acting as photoreductants and photo-oxidants. We find certain stereodifferentiation favoring oxidation of the cis-isomer, in agreement with previous experimental data. Second, we determine the reaction profiles of the ring-opening mechanism of the cationic, neutral, and anionic systems and assess their feasibility based on their energy barrier heights and the stability of the reactants and products. Results show that oxidation largely decreases the ring-opening energy barrier for both stereoisomers, even though the process is forecast as too slow to be competitive. Conversely, one-electron reduction dramatically facilitates the ring opening of the azetidine heterocycle. Considering the overall quantum-chemistry findings, N,N-dimethylaniline is proposed as an efficient photosensitizer to trigger the photoinduced cycloreversion of the DNA lesion model. Full article
(This article belongs to the Special Issue DNA Damage and Repair)
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30 pages, 3750 KiB  
Article
A Mathematical Radiobiological Model (MRM) to Predict Complex DNA Damage and Cell Survival for Ionizing Particle Radiations of Varying Quality
by Spyridon A. Kalospyros, Zacharenia Nikitaki, Ioanna Kyriakou, Michael Kokkoris, Dimitris Emfietzoglou and Alexandros G. Georgakilas
Molecules 2021, 26(4), 840; https://doi.org/10.3390/molecules26040840 - 05 Feb 2021
Cited by 9 | Viewed by 3025
Abstract
Predicting radiobiological effects is important in different areas of basic or clinical applications using ionizing radiation (IR); for example, towards optimizing radiation protection or radiation therapy protocols. In this case, we utilized as a basis the ‘MultiScale Approach (MSA)’ model and developed an [...] Read more.
Predicting radiobiological effects is important in different areas of basic or clinical applications using ionizing radiation (IR); for example, towards optimizing radiation protection or radiation therapy protocols. In this case, we utilized as a basis the ‘MultiScale Approach (MSA)’ model and developed an integrated mathematical radiobiological model (MRM) with several modifications and improvements. Based on this new adaptation of the MSA model, we have predicted cell-specific levels of initial complex DNA damage and cell survival for irradiation with 11Β, 12C, 14Ν, 16Ο, 20Νe, 40Αr, 28Si and 56Fe ions by using only three input parameters (particle’s LET and two cell-specific parameters: the cross sectional area of each cell nucleus and its genome size). The model-predicted survival curves are in good agreement with the experimental ones. The particle Relative Biological Effectiveness (RBE) and Oxygen Enhancement Ratio (OER) are also calculated in a very satisfactory way. The proposed integrated MRM model (within current limitations) can be a useful tool for the assessment of radiation biological damage for ions used in hadron-beam radiation therapy or radiation protection purposes. Full article
(This article belongs to the Special Issue DNA Damage and Repair)
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16 pages, 2415 KiB  
Article
Stacking Effects on Anthraquinone/DNA Charge-Transfer Electronically Excited States
by Gustavo Cárdenas and Juan J. Nogueira
Molecules 2020, 25(24), 5927; https://doi.org/10.3390/molecules25245927 - 15 Dec 2020
Cited by 5 | Viewed by 2983
Abstract
The design of more efficient photosensitizers is a matter of great importance in the field of cancer treatment by means of photodynamic therapy. One of the main processes involved in the activation of apoptosis in cancer cells is the oxidative stress on DNA [...] Read more.
The design of more efficient photosensitizers is a matter of great importance in the field of cancer treatment by means of photodynamic therapy. One of the main processes involved in the activation of apoptosis in cancer cells is the oxidative stress on DNA once a photosensitizer is excited by light. As a consequence, it is very relevant to investigate in detail the binding modes of the chromophore with DNA, and the nature of the electronically excited states that participate in the induction of DNA damage, for example, charge-transfer states. In this work, we investigate the electronic structure of the anthraquinone photosensitizer intercalated into a double-stranded poly(dG-dC) decamer model of DNA. First, the different geometric configurations are analyzed by means of classical molecular dynamics simulations. Then, the excited states for the most relevant poses of anthraquinone inside the binding pocket are computed by an electrostatic-embedding quantum mechanics/molecular mechanics approach, where anthraquinone and one of the nearby guanine residues are described quantum mechanically to take into account intermolecular charge-transfer states. The excited states are characterized as monomer, exciton, excimer, and charge-transfer states based on the analysis of the transition density matrix, and each of these contributions to the total density of states and absorption spectrum is discussed in terms of the stacking interactions. These results are relevant as they represent the footing for future studies on the reactivity of anthraquinone derivatives with DNA and give insights on possible geometrical configurations that potentially favor the oxidative stress of DNA. Full article
(This article belongs to the Special Issue DNA Damage and Repair)
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16 pages, 4175 KiB  
Article
Tracing the Photoaddition of Pharmaceutical Psoralens to DNA
by Janina Diekmann, Isabell Theves, Kristoffer A. Thom and Peter Gilch
Molecules 2020, 25(22), 5242; https://doi.org/10.3390/molecules25225242 - 10 Nov 2020
Cited by 11 | Viewed by 3470
Abstract
The psoralens 8-methoxypsoralen (8-MOP), 4,5′,8-trimethylpsoralen (TMP) and 5-methoxypsoralen (5-MOP) find clinical application in PUVA (psoralen + UVA) therapy. PUVA treats skin diseases like psoriasis and atopic eczema. Psoralens target the DNA of cells. Upon photo-excitation psoralens bind to the DNA base thymine. This [...] Read more.
The psoralens 8-methoxypsoralen (8-MOP), 4,5′,8-trimethylpsoralen (TMP) and 5-methoxypsoralen (5-MOP) find clinical application in PUVA (psoralen + UVA) therapy. PUVA treats skin diseases like psoriasis and atopic eczema. Psoralens target the DNA of cells. Upon photo-excitation psoralens bind to the DNA base thymine. This photo-binding was studied using steady-state UV/Vis and IR spectroscopy as well as nanosecond transient UV/Vis absorption. The experiments show that the photo-addition of 8-MOP and TMP involve the psoralen triplet state and a biradical intermediate. 5-MOP forms a structurally different photo-product. Its formation could not be traced by the present spectroscopic technique. Full article
(This article belongs to the Special Issue DNA Damage and Repair)
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10 pages, 2059 KiB  
Article
Guanine Radicals Generated in Telomeric G-Quadruplexes by Direct Absorption of Low-Energy UV Photons: Effect of Potassium Ions
by Evangelos Balanikas, Akos Banyasz, Gérard Baldacchino and Dimitra Markovitsi
Molecules 2020, 25(9), 2094; https://doi.org/10.3390/molecules25092094 - 30 Apr 2020
Cited by 10 | Viewed by 2659
Abstract
The study deals with the primary species, ejected electrons, and guanine radicals, leading to oxidative damage, that is generated in four-stranded DNA structures (guanine quadruplexes) following photo-ionization by low-energy UV radiation. Performed by nanosecond transient absorption spectroscopy with 266 nm excitation, it focusses [...] Read more.
The study deals with the primary species, ejected electrons, and guanine radicals, leading to oxidative damage, that is generated in four-stranded DNA structures (guanine quadruplexes) following photo-ionization by low-energy UV radiation. Performed by nanosecond transient absorption spectroscopy with 266 nm excitation, it focusses on quadruplexes formed by folding of GGG(TTAGGG)3 single strands in the presence of K+ ions, TEL21/K+. The quantum yield for one-photon ionization (9.4 × 10−3) was found to be twice as high as that reported previously for TEL21/Na+. The overall population of guanine radicals decayed faster, their half times being, respectively, 1.4 and 6.7 ms. Deprotonation of radical cations extended over four orders of magnitude of time; the faster step, concerning 40% of their population, was completed within 500 ns. A reaction intermediate, issued from radicals, whose absorption spectrum peaked around 390 nm, was detected. Full article
(This article belongs to the Special Issue DNA Damage and Repair)
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Review

Jump to: Research

24 pages, 1918 KiB  
Review
DNA Damaged Induced Cell Death in Oocytes
by Jakob Gebel, Marcel Tuppi, Nicole Sänger, Björn Schumacher and Volker Dötsch
Molecules 2020, 25(23), 5714; https://doi.org/10.3390/molecules25235714 - 03 Dec 2020
Cited by 25 | Viewed by 3922
Abstract
The production of haploid gametes through meiosis is central to the principle of sexual reproduction. The genetic diversity is further enhanced by exchange of genetic material between homologous chromosomes by the crossover mechanism. This mechanism not only requires correct pairing of homologous chromosomes [...] Read more.
The production of haploid gametes through meiosis is central to the principle of sexual reproduction. The genetic diversity is further enhanced by exchange of genetic material between homologous chromosomes by the crossover mechanism. This mechanism not only requires correct pairing of homologous chromosomes but also efficient repair of the induced DNA double-strand breaks. Oocytes have evolved a unique quality control system that eliminates cells if chromosomes do not correctly align or if DNA repair is not possible. Central to this monitoring system that is conserved from nematodes and fruit fly to humans is the p53 protein family, and in vertebrates in particular p63. In mammals, oocytes are stored for a long time in the prophase of meiosis I which, in humans, can last more than 50 years. During the entire time of this arrest phase, the DNA damage checkpoint remains active. The treatment of female cancer patients with DNA damaging irradiation or chemotherapeutics activates this checkpoint and results in elimination of the oocyte pool causing premature menopause and infertility. Here, we review the molecular mechanisms of this quality control system and discuss potential therapeutic intervention for the preservation of the oocyte pool during chemotherapy. Full article
(This article belongs to the Special Issue DNA Damage and Repair)
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21 pages, 729 KiB  
Review
Minireview Exploring the Biological Cycle of Vitamin B3 and Its Influence on Oxidative Stress: Further Molecular and Clinical Aspects
by Bogdan Doroftei, Ovidiu-Dumitru Ilie, Roxana-Oana Cojocariu, Alin Ciobica, Radu Maftei, Delia Grab, Emil Anton, Jack McKenna, Nitasha Dhunna and Gabriela Simionescu
Molecules 2020, 25(15), 3323; https://doi.org/10.3390/molecules25153323 - 22 Jul 2020
Cited by 20 | Viewed by 8500
Abstract
Vitamin B3, or niacin, is one of the most important compounds of the B-vitamin complex. Recent reports have demonstrated the involvement of vitamin B3 in a number of pivotal functions which ensure that homeostasis is maintained. In addition, the intriguing nature of its [...] Read more.
Vitamin B3, or niacin, is one of the most important compounds of the B-vitamin complex. Recent reports have demonstrated the involvement of vitamin B3 in a number of pivotal functions which ensure that homeostasis is maintained. In addition, the intriguing nature of its synthesis and the underlying mechanism of action of vitamin B3 have encouraged further studies aimed at deepening our understanding of the close link between the exogenous supply of B3 and how it activates dependent enzymes. This crucial role can be attributed to the gut microflora and its ability to shape human behavior and development by mediating the bioavailability of metabolites. Recent studies have indicated a possible interconnection between the novel coronavirus and commensal bacteria. As such, we have attempted to explain how the gastrointestinal deficiencies displayed by SARS-CoV-2-infected patients arise. It seems that the stimulation of a proinflammatory cascade and the production of large amounts of reactive oxygen species culminates in the subsequent loss of host eubiosis. Studies of the relationhip between ROS, SARS-CoV-2, and gut flora are sparse in the current literature. As an integrated component, oxidative stress (OS) has been found to negatively influence host eubiosis, in vitro fertilization outcomes, and oocyte quality, but to act as a sentinel against infections. In conclusion, research suggests that in the future, a healthy diet may be considered a reliable tool for maintaining and optimizing our key internal parameters. Full article
(This article belongs to the Special Issue DNA Damage and Repair)
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28 pages, 2755 KiB  
Review
Resolving DNA Damage: Epigenetic Regulation of DNA Repair
by Panagiotis Karakaidos, Dimitris Karagiannis and Theodoros Rampias
Molecules 2020, 25(11), 2496; https://doi.org/10.3390/molecules25112496 - 27 May 2020
Cited by 33 | Viewed by 8422
Abstract
Epigenetic research has rapidly evolved into a dynamic field of genome biology. Chromatin regulation has been proved to be an essential aspect for all genomic processes, including DNA repair. Chromatin structure is modified by enzymes and factors that deposit, erase, and interact with [...] Read more.
Epigenetic research has rapidly evolved into a dynamic field of genome biology. Chromatin regulation has been proved to be an essential aspect for all genomic processes, including DNA repair. Chromatin structure is modified by enzymes and factors that deposit, erase, and interact with epigenetic marks such as DNA and histone modifications, as well as by complexes that remodel nucleosomes. In this review we discuss recent advances on how the chromatin state is modulated during this multi-step process of damage recognition, signaling, and repair. Moreover, we examine how chromatin is regulated when different pathways of DNA repair are utilized. Furthermore, we review additional modes of regulation of DNA repair, such as through the role of global and localized chromatin states in maintaining expression of DNA repair genes, as well as through the activity of epigenetic enzymes on non-nucleosome substrates. Finally, we discuss current and future applications of the mechanistic interplays between chromatin regulation and DNA repair in the context cancer treatment. Full article
(This article belongs to the Special Issue DNA Damage and Repair)
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