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Recent Advances on DNA Damage Response: From Molecular Mechanisms to Therapeutic Opportunities

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

Deadline for manuscript submissions: 30 June 2024 | Viewed by 5257

Special Issue Editors

Dr. Alessandra Di Masi

E-Mail Website
Guest Editor
Department of Sciences, Roma Tre University, Viale Guglielmo Marconi 446, 00146 Rome, Italy
Interests: DNA damage response pathways; cancer; acute myeloid leukemia; small molecular inhibitors; DNA-related disorders
Special Issues, Collections and Topics in MDPI journals
Dr. Francesco Berardinelli

E-Mail Website
Guest Editor
Dipartimento di Scienze and INFN, Università Roma Tre, 00146 Roma, Italy
Interests: genome stability; telomeres; DNA damage response pathways; cancer; glioblastoma; G-quadruplex ligands; small-molecular inhibitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cells are continuously exposed to endogenous and exogenous DNA-damaging agents. To properly protect the genome, all types of DNA lesions are repaired by complex DNA damage response (DDR) pathways that include cell cycle arrest as well as transcriptional and post-translational activation of genes and proteins, including those associated with DNA repair, senescence and programmed cell death. The DDR acts through sensors, transducers, and effectors that orchestrate the spatial and temporal order of DNA/protein and protein/protein interactions to allow the maintenance of genomic stability and integrity. Improper DDR may result in various diseases, including cancer, premature aging, immunodeficiencies, chronic inflammatory conditions, and autoimmune disorders. Understanding the broader roles of DDR in cell and tissue homeostasis has brought key molecular mechanisms into sharper focus, providing valuable information for the identification of novel druggable targets. In this Special Issue, original studies, review articles, case reports, and commentaries focused on the molecular mechanisms and therapeutic strategies related to DDR are warmly welcome.

Dr. Alessandra Di Masi
Dr. Francesco Berardinelli
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

  • DNA damage
  • DNA repair
  • genomic stability
  • DDR targets
  • drug
  • cancer
  • aging
  • human disease

Published Papers (3 papers)

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Research

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13 pages, 1389 KiB  
Communication
Chronological Age and DNA Damage Accumulation in Blood Mononuclear Cells: A Linear Association in Healthy Humans after 50 Years of Age
by Nikolaos I. Vlachogiannis, Panagiotis A. Ntouros, Maria Pappa, Evrydiki Kravvariti, Evangelia Georgia Kostaki, Georgios E. Fragoulis, Christina Papanikolaou, Dimitra Mavroeidi, Vasiliki-Kalliopi Bournia, Stylianos Panopoulos, Katerina Laskari, Aikaterini Arida, Vassilis G. Gorgoulis, Maria G. Tektonidou, Dimitrios Paraskevis, Petros P. Sfikakis and Vassilis L. Souliotis
Int. J. Mol. Sci. 2023, 24(8), 7148; https://doi.org/10.3390/ijms24087148 - 12 Apr 2023
Viewed by 1468
Abstract
Aging is characterized by the progressive deregulation of homeostatic mechanisms causing the accumulation of macromolecular damage, including DNA damage, progressive decline in organ function and chronic diseases. Since several features of the aging phenotype are closely related to defects in the DNA damage [...] Read more.
Aging is characterized by the progressive deregulation of homeostatic mechanisms causing the accumulation of macromolecular damage, including DNA damage, progressive decline in organ function and chronic diseases. Since several features of the aging phenotype are closely related to defects in the DNA damage response (DDR) network, we have herein investigated the relationship between chronological age and DDR signals in peripheral blood mononuclear cells (PBMCs) from healthy individuals. DDR-associated parameters, including endogenous DNA damage (single-strand breaks and double-strand breaks (DSBs) measured by the alkaline comet assay (Olive Tail Moment (OTM); DSBs-only by γH2AX immunofluorescence staining), DSBs repair capacity, oxidative stress, and apurinic/apyrimidinic sites were evaluated in PBMCs of 243 individuals aged 18–75 years, free of any major comorbidity. While OTM values showed marginal correlation with age until 50 years (rs = 0.41, p = 0.11), a linear relationship was observed after 50 years (r = 0.95, p < 0.001). Moreover, individuals older than 50 years showed increased endogenous DSBs levels (γH2Ax), higher oxidative stress, augmented apurinic/apyrimidinic sites and decreased DSBs repair capacity than those with age lower than 50 years (all p < 0.001). Results were reproduced when we examined men and women separately. Prospective studies confirming the value of DNA damage accumulation as a biomarker of aging, as well as the presence of a relevant agethreshold, are warranted. Full article
(This article belongs to the Special Issue Recent Advances on DNA Damage Response: From Molecular Mechanisms to Therapeutic Opportunities)
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Review

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20 pages, 954 KiB  
Review
Novel Cellular Functions of ATR for Therapeutic Targeting: Embryogenesis to Tumorigenesis
by Himadri Biswas, Yetunde Makinwa and Yue Zou
Int. J. Mol. Sci. 2023, 24(14), 11684; https://doi.org/10.3390/ijms241411684 - 20 Jul 2023
Cited by 2 | Viewed by 1875
Abstract
The DNA damage response (DDR) is recognized as having an important role in cancer growth and treatment. ATR (ataxia telangiectasia mutated and Rad3-related) kinase, a major regulator of DDR, has shown significant therapeutic potential in cancer treatment. ATR inhibitors have shown anti-tumor effectiveness, [...] Read more.
The DNA damage response (DDR) is recognized as having an important role in cancer growth and treatment. ATR (ataxia telangiectasia mutated and Rad3-related) kinase, a major regulator of DDR, has shown significant therapeutic potential in cancer treatment. ATR inhibitors have shown anti-tumor effectiveness, not just as monotherapies but also in enhancing the effects of standard chemotherapy, radiation, and immunotherapy. The biological basis of ATR is examined in this review, as well as its functional significance in the development and therapy of cancer, and the justification for inhibiting this target as a therapeutic approach, including an assessment of the progress and status of previous decades’ development of effective and selective ATR inhibitors. The current applications of these inhibitors in preclinical and clinical investigations as single medicines or in combination with chemotherapy, radiation, and immunotherapy are also fully reviewed. This review concludes with some insights into the many concerns highlighted or identified with ATR inhibitors in both the preclinical and clinical contexts, as well as potential remedies proposed. Full article
(This article belongs to the Special Issue Recent Advances on DNA Damage Response: From Molecular Mechanisms to Therapeutic Opportunities)
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14 pages, 309 KiB  
Review
Standards for Quantitative Measurement of DNA Damage in Mammalian Cells
by Donald H. Atha and Vytas Reipa
Int. J. Mol. Sci. 2023, 24(6), 5427; https://doi.org/10.3390/ijms24065427 - 12 Mar 2023
Viewed by 1370
Abstract
As the potential applications of DNA diagnostics continue to expand, there is a need for improved methods and standards for DNA analysis. This report describes several methods that could be considered for the production of reference materials for the quantitative measurement of DNA [...] Read more.
As the potential applications of DNA diagnostics continue to expand, there is a need for improved methods and standards for DNA analysis. This report describes several methods that could be considered for the production of reference materials for the quantitative measurement of DNA damage in mammalian cells. With the focus on DNA strand breaks, potentially useful methods for assessing DNA damage in mammalian cells are reviewed. The advantages and limitations of each method, as well as additional concerns with respect to reference material development, are also discussed. In conclusion, we outline strategies for developing candidate DNA damage reference materials that could be adopted by research laboratories in a wide variety of applications. Full article
(This article belongs to the Special Issue Recent Advances on DNA Damage Response: From Molecular Mechanisms to Therapeutic Opportunities)
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