Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
10.5
5.2
Journals
Cells
Special Issues
Epigenetics and DNA Repair: Regulatory Mechanisms and Therapeutic Opportunities
share announcement

Epigenetics and DNA Repair: Regulatory Mechanisms and Therapeutic Opportunities

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: 15 December 2025 | Viewed by 9019

Special Issue Editor

Prof. Dr. Vasily M. Studitsky

E-Mail Website
Guest Editor
1. Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
2. Fox Chase Cancer Center, Philadelphia, PA 19111-2497, USA
Interests: mechanisms of transcription and replication in chromatin; mechanisms of histone chaperone action in chromatin
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In eukaryotic cells, DNA damage occurs in chromatin, a DNA–protein complex that strongly compacts DNA. The packaging of DNA in chromatin creates a strong barrier against DNA-damage-response proteins that must interact with DNA to prevent mutations and cell death. Therefore, during DNA repair, chromatin’s structure is extensively and reversibly modified by factors such as chromatin remodelers, histone variants, and histone post-translational modifications ensure access of the regulatory proteins and DNA repair machinery to their DNA targets. The epigenetic factors that modulate the chromatin environment strongly contribute to an efficient DNA damage response. This highly dynamic process of DNA repair in the chromatin environment is essential for the functioning and survival of the cell. Recent studies have revealed a multitude of factors participating in DNA repair; however, researchers have not yet fully established their mechanisms of action, interacting partners, and roles in the regulation of cellular metabolism and the development of human diseases.

In this Special Issue of Cells, we invite researchers to present original studies and state-of-the-art reviews on the mechanisms and regulation of DNA repair in a chromatin environment, and to discuss their data and opinions.

Prof. Dr. Vasily M. Studitsky
Guest Editor

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. Cells 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
  • epigenetics
  • chromatin
  • remodeling

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

19 pages, 2121 KB  
Article
Non-Classical H1-like PARP1 Binding to Chromatosome
by Daria Koshkina, Natalya Maluchenko, Dmitry Nilov, Alexander Lyubitelev, Anna Korovina, Sergey Pushkarev, Grigoriy Armeev, Mikhail Kirpichnikov, Vasily Studitsky and Alexey Feofanov
Cells 2025, 14(17), 1309; https://doi.org/10.3390/cells14171309 - 25 Aug 2025
Viewed by 949
Abstract
Poly(ADP-ribose)polymerase 1 (PARP1) is an enzyme that interacts with chromatin during DNA repair and transcription processes; the molecular mechanisms of these processes remain to be determined. Previously, we have shown that PARP1 can bind to and reorganize nucleosomes using two modes of interaction [...] Read more.
Poly(ADP-ribose)polymerase 1 (PARP1) is an enzyme that interacts with chromatin during DNA repair and transcription processes; the molecular mechanisms of these processes remain to be determined. Previously, we have shown that PARP1 can bind to and reorganize nucleosomes using two modes of interaction with a mono-nucleosome, which are realized through PARP1 binding to the ends of linker DNA and to the nucleosome core. Here, it is shown that the latter mode of binding induces the reorganization of nucleosome structure and is more stable under the conditions of poly(ADP-ribosyl)ation (PARylation). The initial nucleosome structure is fully recovered after the dissociation of autoPARylated PARP1. The competition between PARP1 and linker histone H1.0 for binding to a nucleosome is mediated by the PARP1-H1.0 interaction and is affected by the length of linker DNA fragments. Longer linkers stabilize H1.0-nucleosome complexes, while shorter linkers facilitate displacement of H1.0 from the chromatosome by PARP1. PARylation removes both H1.0 and PARP1 from the complexes with nucleosomes. The data suggest that the H1.0 displacement from chromatin by PARP1 that is likely modulated by the density of nucleosomes might reduce chromatin compaction and facilitate access of PARP1-dependent DNA repair and transcription factors to nucleosome and inter-nucleosomal DNA. Full article
(This article belongs to the Special Issue Epigenetics and DNA Repair: Regulatory Mechanisms and Therapeutic Opportunities)
►▼ Show Figures

Figure 1

14 pages, 1638 KB  
Article
The Consequence of the Presence of Ribonucleotide for ds-DNA’s Electronic Properties: Preliminary Theoretical Studies
by Boleslaw T. Karwowski
Cells 2025, 14(12), 881; https://doi.org/10.3390/cells14120881 - 11 Jun 2025
Viewed by 786
Abstract
The genome is continuously exposed to different harmful factors whose activity causes different types of lesions. On the other hand, during the DNA replication process, a ribonucleoside (rN) can be inserted more frequently than the occurrence of DNA damage in the genome. Notably, [...] Read more.
The genome is continuously exposed to different harmful factors whose activity causes different types of lesions. On the other hand, during the DNA replication process, a ribonucleoside (rN) can be inserted more frequently than the occurrence of DNA damage in the genome. Notably, it can be expected that their presence and chemical lability change the electronic properties of the double helix. In this study, a short ds-oligo with a single rN was taken into consideration. The ground-state molecular geometry was obtained at the M06-2x/D95* level of theory in the aqueous phase, while the energy and vertical and adiabatic electron affinity and ionisation potential were obtained at M06-2x/6-31++G**. The obtained results indicate that the 3′,5′-phosphodiester bond cleavage is favourable after the adiabatic cation and anion states are achieved by ds-DNA. Moreover, the lowest ionisation potential and highest electron affinity of 2.76 and 5.55 eV, respectively, which make it a suitable endpoint for electrons and holes, have been found for the final product that contains a single-strand break. Additionally, after the internucleotide 3′,5′→2′,5′ bond migration process, proton-coupled electron transfer was found to occur. In this article, the electronic properties of short ds-DNA fragments with ribonucleoside inserts are reported for the first time. The obtained results suggest that rNs can play a significant role in the communication of repair and replication proteins via electron transfer, especially after rearrangement. Moreover, the discussed internucleotide bond stability changes after one-electron oxidation or reduction and can support new radiotherapy strategies that are safer and more effective. Further theoretical and experimental studies are highly warranted. Full article
(This article belongs to the Special Issue Epigenetics and DNA Repair: Regulatory Mechanisms and Therapeutic Opportunities)
►▼ Show Figures

Figure 1

16 pages, 2516 KB  
Article
A Knockout of Poly(ADP-Ribose) Polymerase 1 in a Human Cell Line: An Influence on Base Excision Repair Reactions in Cellular Extracts
by Svetlana N. Khodyreva, Ekaterina S. Ilina, Nadezhda S. Dyrkheeva, Alina S. Kochetkova, Alexandra A. Yamskikh, Ekaterina A. Maltseva, Anastasia A. Malakhova, Sergey P. Medvedev, Suren M. Zakian and Olga I. Lavrik
Cells 2024, 13(4), 302; https://doi.org/10.3390/cells13040302 - 6 Feb 2024
Cited by 1 | Viewed by 2460
Abstract
Base excision repair (BER) is the predominant pathway for the removal of most forms of hydrolytic, oxidative, and alkylative DNA lesions. The precise functioning of BER is achieved via the regulation of each step by regulatory/accessory proteins, with the most important of them [...] Read more.
Base excision repair (BER) is the predominant pathway for the removal of most forms of hydrolytic, oxidative, and alkylative DNA lesions. The precise functioning of BER is achieved via the regulation of each step by regulatory/accessory proteins, with the most important of them being poly(ADP-ribose) polymerase 1 (PARP1). PARP1′s regulatory functions extend to many cellular processes including the regulation of mRNA stability and decay. PARP1 can therefore affect BER both at the level of BER proteins and at the level of their mRNAs. Systematic data on how the PARP1 content affects the activities of key BER proteins and the levels of their mRNAs in human cells are extremely limited. In this study, a CRISPR/Cas9-based technique was used to knock out the PARP1 gene in the human HEK 293FT line. The obtained cell clones with the putative PARP1 deletion were characterized by several approaches including PCR analysis of deletions in genomic DNA, Sanger sequencing of genomic DNA, quantitative PCR analysis of PARP1 mRNA, Western blot analysis of whole-cell-extract (WCE) proteins with anti-PARP1 antibodies, and PAR synthesis in WCEs. A quantitative PCR analysis of mRNAs coding for BER-related proteins—PARP2, uracil DNA glycosylase 2, apurinic/apyrimidinic endonuclease 1, DNA polymerase β, DNA ligase III, and XRCC1—did not reveal a notable influence of the PARP1 knockout. The corresponding WCE catalytic activities evaluated in parallel did not differ significantly between the mutant and parental cell lines. No noticeable effect of poly(ADP-ribose) synthesis on the activity of the above WCE enzymes was revealed either. Full article
(This article belongs to the Special Issue Epigenetics and DNA Repair: Regulatory Mechanisms and Therapeutic Opportunities)
►▼ Show Figures

Figure 1

20 pages, 5833 KB  
Article
Individual Contributions of Amido Acid Residues Tyr122, Ile168, and Asp173 to the Activity and Substrate Specificity of Human DNA Dioxygenase ABH2
by Anastasiia T. Davletgildeeva, Timofey E. Tyugashev, Mingxing Zhao, Nikita A. Kuznetsov, Alexander A. Ishchenko, Murat Saparbaev and Aleksandra A. Kuznetsova
Cells 2023, 12(14), 1839; https://doi.org/10.3390/cells12141839 - 13 Jul 2023
Cited by 1 | Viewed by 1752
Abstract
Human Fe(II)/α-ketoglutarate-dependent dioxygenase ABH2 plays a crucial role in the direct reversal repair of nonbulky alkyl lesions in DNA nucleobases, e.g., N1-methyladenine (m1A), N3-methylcytosine (m3C), and some etheno derivatives. Moreover, ABH2 is capable of a [...] Read more.
Human Fe(II)/α-ketoglutarate-dependent dioxygenase ABH2 plays a crucial role in the direct reversal repair of nonbulky alkyl lesions in DNA nucleobases, e.g., N1-methyladenine (m1A), N3-methylcytosine (m3C), and some etheno derivatives. Moreover, ABH2 is capable of a less efficient oxidation of an epigenetic DNA mark called 5-methylcytosine (m5C), which typically is a specific target of DNA dioxygenases from the TET family. In this study, to elucidate the mechanism of the substrate specificity of ABH2, we investigated the role of several active-site amino acid residues. Functional mapping of the lesion-binding pocket was performed through the analysis of the functions of Tyr122, Ile168, and Asp173 in the damaged base recognition mechanism. Interactions of wild-type ABH2, or its mutants Y122A, I168A, or D173A, with damaged DNA containing the methylated base m1A or m3C or the epigenetic marker m5C were analyzed by molecular dynamics simulations and kinetic assays. Comparative analysis of the enzymes revealed an effect of the substitutions on DNA binding and on catalytic activity. Obtained data clearly demonstrate the effect of the tested amino acid residues on the catalytic activity of the enzymes rather than the DNA-binding ability. Taken together, these data shed light on the molecular and kinetic consequences of the substitution of active-site residues for the mechanism of the substrate recognition. Full article
(This article belongs to the Special Issue Epigenetics and DNA Repair: Regulatory Mechanisms and Therapeutic Opportunities)
►▼ Show Figures

Figure 1

17 pages, 6118 KB  
Article
The Activity of Natural Polymorphic Variants of Human DNA Polymerase β Having an Amino Acid Substitution in the Transferase Domain
by Olga A. Kladova, Timofey E. Tyugashev, Elena S. Mikushina, Nikita A. Kuznetsov, Daria S. Novopashina and Aleksandra A. Kuznetsova
Cells 2023, 12(9), 1300; https://doi.org/10.3390/cells12091300 - 2 May 2023
Cited by 3 | Viewed by 2200
Abstract
To maintain the integrity of the genome, there is a set of enzymatic systems, one of which is base excision repair (BER), which includes sequential action of DNA glycosylases, apurinic/apyrimidinic endonucleases, DNA polymerases, and DNA ligases. Normally, BER works efficiently, but the enzymes [...] Read more.
To maintain the integrity of the genome, there is a set of enzymatic systems, one of which is base excision repair (BER), which includes sequential action of DNA glycosylases, apurinic/apyrimidinic endonucleases, DNA polymerases, and DNA ligases. Normally, BER works efficiently, but the enzymes themselves (whose primary function is the recognition and removal of damaged bases) are subject to amino acid substitutions owing to natural single-nucleotide polymorphisms (SNPs). One of the enzymes in BER is DNA polymerase β (Polβ), whose function is to fill gaps in DNA with complementary dNMPs. It is known that many SNPs can cause an amino acid substitution in this enzyme and a significant decrease in the enzymatic activity. In this study, the activity of four natural variants of Polβ, containing substitution E154A, G189D, M236T, or R254I in the transferase domain, was analyzed using molecular dynamics simulations and pre-steady-state kinetic analyses. It was shown that all tested substitutions lead to a significant reduction in the ability to form a complex with DNA and with incoming dNTP. The G189D substitution also diminished Polβ catalytic activity. Thus, a decrease in the activity of studied mutant forms may be associated with an increased risk of damage to the genome. Full article
(This article belongs to the Special Issue Epigenetics and DNA Repair: Regulatory Mechanisms and Therapeutic Opportunities)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop