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Biomolecules
Special Issues
Molecular Mechanisms in DNA and RNA Damage and Repair
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Molecular Mechanisms in DNA and RNA Damage and Repair

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biomarkers".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 3636

Special Issue Editors

Dr. Marino J. E. Resendiz

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Guest Editor
Department of Chemistry, University of Colorado Denver, Denver, CO, USA
Interests: structure–function relationships of chemically modified RNA; 8-oxoG and 8-oxopurines within RNA; ribonucleolytic activity of oxidized RNA; chemical synthesis of modified RNA and DNA
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Chryssostomos Chatgilialoglu

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Guest Editor
1. Institute for Organic Synthesis and Photoreactivity, National Research Council, Bologna, Italy
2. Center for Advanced Technology, Adam Mickiewicz University, Poznan, Poland
Interests: free radical chemistry; biomimetic chemistry; molecular mechanism; oxidative DNA damage; lipid modification; fatty acid-based lipidomics; biomarkers of radical stress
Special Issues, Collections and Topics in MDPI journals
Dr. Yuan Liu

E-Mail Website
Guest Editor
Department of Chemistry and Biochemistry, Biochemistry Ph.D. Program, and Biomolecular Sciences Institute, Florida International University, Miami, FL, USA
Interests: oxidative DNA and RNA damage; DNA base excision repair; RNA damage repair; RNA modifications and DNA repair; trinucleotide repeat instability and repeat expansion diseases; gene-targeted editing of DNA repair; epigenetics; epitranscriptomic modifications via CRISPR/Cas9-based systems

Special Issue Information

Dear Colleagues,

Reactive oxygen species (ROS) are generated through normal intracellular metabolism and function as physiological signaling species. Some of these reactive species are known for their reactivity and ability to cause DNA and RNA damage. These damages may also be induced by other environmentally derived insults such as ionizing radiation, UV light, and chemical mutagens. DNA damage may challenge the repair machinery of the cell. Indeed, enzymatic systems such as base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) are known to remove the majority of DNA lesions and safeguard the integrity of the genome. Recent studies have demonstrated that BER enzymes and translesion DNA polymerases can also process RNA, suggesting that a novel mechanism of repairing RNA damage by DNA repair may exist. However, DNA and RNA lesions may accumulate in cells and tissues, mainly due to the progressive loss of protective systems and consequent poor repair, as they occur in the aging process. Thus, it is important to understand the intracellular handling of these chemically modified biopolymers. Also, repair enzymatic deficiencies can give rise to the accumulation of damage to cellular components that are linked to specific pathologies. The identification of underlying molecular mechanisms of oxidative DNA and RNA damage and their repair will lead to the development of new biomarkers and therapeutic targets for disease diagnostics and treatments.

This Special Issue covers various aspects of DNA and RNA damage and repair research: DNA and RNA oxidation products, molecular mechanisms, biomarker identification, defense and repair strategies, and therapeutic strategies for diseases associated with oxidative DNA and RNA damage. 

Research articles and reviews related to these topics are welcome.

Dr. Marino J. E. Resendiz
Prof. Dr. Chryssostomos Chatgilialoglu
Dr. Yuan Liu
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. Biomolecules is an international peer-reviewed open access monthly 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

  • reactive oxygen species
  • DNA damage
  • DNA repair
  • RNA damage
  • RNA repair
  • molecular mechanisms
  • biomarkers
  • antioxidant and redox strategies
  • oxidative stress

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Published Papers (3 papers)

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Research

9 pages, 2102 KiB  
Communication
Tissue-Specific Effects of Aging on Repeat-Mediated Mutation Hotspots In Vivo
by Alexandra M. D’Amico, Tonia T. Li and Karen M. Vasquez
Biomolecules 2024, 14(11), 1453; https://doi.org/10.3390/biom14111453 - 16 Nov 2024
Viewed by 281
Abstract
Aging constitutes complex and dynamic alterations in molecular and physiological processes and is associated with numerous disorders, in part due to increased genetic instability. The aging population is projected to double by 2050, underscoring the urgent need to better understand the relationships between [...] Read more.
Aging constitutes complex and dynamic alterations in molecular and physiological processes and is associated with numerous disorders, in part due to increased genetic instability. The aging population is projected to double by 2050, underscoring the urgent need to better understand the relationships between aging and age-related disorders. Repetitive DNA elements are intrinsic sources of genetic instability and have been found to co-localize with mutation hotspots in human cancer genomes. In this study, we explored the relationship between aging and DNA repeat-mediated genetic instability in vivo using an H-DNA-forming mirror-repeat sequence from the cancer-associated human c-MYC gene. Utilizing a unique mutation-reporter mouse model, we observed tissue-specific effects of aging on H-DNA-induced genetic instability, with mutation frequencies increasing in spleen tissues and remaining unchanged in testis tissues. Analysis of the mutation spectra revealed large deletion mutations as the primary contributor to increasing H-DNA-induced mutations, supported by increased cleavage activity of H-DNA structures in aged spleen tissues. Our findings demonstrate that aging has distinct tissue-specific effects on repeat-mediated, cancer-associated mutations, providing insights into the complex relationship between aging and cancer. Full article
(This article belongs to the Special Issue Molecular Mechanisms in DNA and RNA Damage and Repair)
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20 pages, 2246 KiB  
Article
DNA Base Damage Repair Crosstalks with Chromatin Structures to Contract Expanded GAA Repeats in Friedreich’s Ataxia
by Yanhao Lai, Nicole Diaz, Rhyisa Armbrister, Irina Agoulnik and Yuan Liu
Biomolecules 2024, 14(7), 809; https://doi.org/10.3390/biom14070809 - 8 Jul 2024
Viewed by 1393
Abstract
Trinucleotide repeat (TNR) expansion is the cause of over 40 neurodegenerative diseases, including Huntington’s disease and Friedreich’s ataxia (FRDA). There are no effective treatments for these diseases due to the poor understanding of molecular mechanisms underlying somatic TNR expansion and contraction in neural [...] Read more.
Trinucleotide repeat (TNR) expansion is the cause of over 40 neurodegenerative diseases, including Huntington’s disease and Friedreich’s ataxia (FRDA). There are no effective treatments for these diseases due to the poor understanding of molecular mechanisms underlying somatic TNR expansion and contraction in neural systems. We and others have found that DNA base excision repair (BER) actively modulates TNR instability, shedding light on the development of effective treatments for the diseases by contracting expanded repeats through DNA repair. In this study, temozolomide (TMZ) was employed as a model DNA base damaging agent to reveal the mechanisms of the BER pathway in modulating GAA repeat instability at the frataxin (FXN) gene in FRDA neural cells and transgenic mouse mice. We found that TMZ induced large GAA repeat contraction in FRDA mouse brain tissue, neurons, and FRDA iPSC-differentiated neural cells, increasing frataxin protein levels in FRDA mouse brain and neural cells. Surprisingly, we found that TMZ could also inhibit H3K9 methyltransferases, leading to open chromatin and increasing ssDNA breaks and recruitment of the key BER enzyme, pol β, on the repeats in FRDA neural cells. We further demonstrated that the H3K9 methyltransferase inhibitor BIX01294 also induced the contraction of the expanded repeats and increased frataxin protein in FRDA neural cells by opening the chromatin and increasing the endogenous ssDNA breaks and recruitment of pol β on the repeats. Our study provides new mechanistic insight illustrating that inhibition of H3K9 methylation can crosstalk with BER to induce GAA repeat contraction in FRDA. Our results will open a new avenue for developing novel gene therapy by targeting histone methylation and the BER pathway for repeat expansion diseases. Full article
(This article belongs to the Special Issue Molecular Mechanisms in DNA and RNA Damage and Repair)
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14 pages, 2593 KiB  
Article
BUB1 Inhibition Sensitizes TNBC Cell Lines to Chemotherapy and Radiotherapy
by Sushmitha Sriramulu, Shivani Thoidingjam, Farzan Siddiqui, Stephen L. Brown, Benjamin Movsas, Eleanor Walker and Shyam Nyati
Biomolecules 2024, 14(6), 625; https://doi.org/10.3390/biom14060625 - 25 May 2024
Cited by 2 | Viewed by 1429
Abstract
BUB1 is overexpressed in most human solid cancers, including breast cancer. Higher BUB1 levels are associated with a poor prognosis, especially in patients with triple-negative breast cancer (TNBC). Women with TNBC often develop resistance to chemotherapy and radiotherapy, which are still the mainstay [...] Read more.
BUB1 is overexpressed in most human solid cancers, including breast cancer. Higher BUB1 levels are associated with a poor prognosis, especially in patients with triple-negative breast cancer (TNBC). Women with TNBC often develop resistance to chemotherapy and radiotherapy, which are still the mainstay of treatment for TNBC. Our previous studies demonstrated that a BUB1 kinase inhibitor (BAY1816032) reduced tumor cell proliferation and significantly enhanced radiotherapy efficacy in TNBC. In this study, we evaluated the effectiveness of BAY1816032 with a PARP inhibitor (olaparib), platinum agent (cisplatin), and microtubule poison (paclitaxel) alone or in combination with radiotherapy using cytotoxicity and clonogenic survival assays. BUB1 inhibitors sensitized BRCA1/2 wild-type SUM159 and MDA-MB-231 cells to olaparib, cisplatin, and paclitaxel synergistically (combination index; CI < 1). BAY1816032 significantly increased the radiation sensitization of SUM159 and MDA-MB-231 by olaparib, cisplatin, or paclitaxel at non-toxic concentrations (doses well below the IC50 concentrations). Importantly, the small molecular inhibitor of BUB1 synergistically (CI < 1) sensitized the BRCA mutant TNBC cell line HCC1937 to olaparib. Furthermore, the BUB1 inhibitor significantly increased the radiation enhancement ratio (rER) in HCC1937 cells (rER 1.34) compared to either agent alone (BUB1i rER 1.19; PARPi rER 1.04). The data presented here are significant as they provide proof that inhibition of BUB1 kinase activity sensitizes TNBC cell lines to a PARP inhibitor and radiation, irrespective of BRCA1/2 mutation status. Due to the ability of the BUB1 inhibitor to sensitize TNBC to different classes of drugs (platinum, PARPi, microtubule depolarization inhibitors), this work strongly supports the role of BUB1 as a novel molecular target to improve chemoradiation efficacy in TNBC and provides a rationale for the clinical evaluation of BAY1816032 as a chemosensitizer and chemoradiosensitizer in TNBC. Full article
(This article belongs to the Special Issue Molecular Mechanisms in DNA and RNA Damage and Repair)
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