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DNA Damage and Repair in Biology and Medicine 2.0

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: closed (15 April 2024) | Viewed by 4485

Special Issue Editors


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Department of Biochemistry and Molecular Biology, Faculty of Medicine and Odontology-INCLIVA, Service of Clinical Analysis, Dr. Peset University Hospital -FISABIO, University of Valencia, Avda. Blasco Ibañez 15, 36010 Valencia, Spain
Interests: oxidative stress-induced DNA damage and repair and its repair mechanisms in cardiometabolic and cancer diseases
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Guest Editor
Endocrinology and Nutrition Department, University Hospital Dr Peset-FISABIO, 46017 Valencia, Spain
Interests: oxidative stress; metabolism; obesity; mitochondria; inflammation; functional foods
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite its strategic location and apparent protection, the integrity of genetic material is the result of a continuous and delicate balance between the mechanisms that induce its injury and those in charge of its repair, whose effectiveness is vital for the normal functioning of the cells and the perpetuity in the transmission of the genetic message in a faithful way. The modalities and mechanisms of DNA damage are very varied, including different forms of structural modification and functional alteration. Together with exogenous factors, such as those induced by chemical agents and ionizing radiation, cells must cope with a rate of genetic damage of 103 to 106 impacts per cell a day, to which normal aerobic metabolism contributes, with the production of reactive species of oxygen (ROS) (3–5% of breathed oxygen) and the consequent alteration in the redox balance, which may have profound effects on the regulation of cell signaling pathways. In DNA molecule structure, many of these lesions can stop replication and alter or inhibit gene transcription. Other lesions, if not repaired before replication takes place, may induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. Genomic instability is an essential step in the development of age-associated comorbidities, such as cardiometabolic disorders, tissue failure, and tumor processes. Higher animals, microorganisms, and plants are susceptible to this potential hazard. Fortunately, evolution has allowed for the development of a plethora of diverse, specific, and efficient DNA repair systems, under the control of multiple molecules and transcriptional factors. The TP53 protein, also known as the guardian of the genome, together with other onco and tumor-suppressor proteins are representative examples.

It is vitally important to know, in detail, both the mechanisms that lead to genetic instability and those that prevent and repair it. In this sense, the Special Issue "DNA Damage and Repair in Biology and Medicine" aims to bring together contributions by research groups that shed new light on their molecular mechanisms and future perspectives on their translational applications.

Prof. Dr. Guillermo T. Sáez
Dr. Celia Banuls
Guest Editors

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Published Papers (2 papers)

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Research

19 pages, 10168 KiB  
Article
Mismatch Repair Protein Msh2 Is Necessary for Macronuclear Stability and Micronuclear Division in Tetrahymena thermophila
by Lin Wang, Yuhuan Xue, Sitong Yang, Tao Bo, Jing Xu and Wei Wang
Int. J. Mol. Sci. 2023, 24(13), 10559; https://doi.org/10.3390/ijms241310559 - 23 Jun 2023
Cited by 1 | Viewed by 1667
Abstract
Mismatch repair (MMR) is a conserved mechanism that is primarily responsible for the repair of DNA mismatches during DNA replication. Msh2 forms MutS heterodimer complexes that initiate the MMR in eukaryotes. The function of Msh2 is less clear under different chromatin structures. Tetrahymena [...] Read more.
Mismatch repair (MMR) is a conserved mechanism that is primarily responsible for the repair of DNA mismatches during DNA replication. Msh2 forms MutS heterodimer complexes that initiate the MMR in eukaryotes. The function of Msh2 is less clear under different chromatin structures. Tetrahymena thermophila contains a transcriptionally active macronucleus (MAC) and a transcriptionally silent micronucleus (MIC) in the same cytoplasm. Msh2 is localized in the MAC and MIC during vegetative growth. Msh2 is localized in the perinuclear region around the MIC and forms a spindle-like structure as the MIC divides. During the early conjugation stage, Msh2 is localized in the MIC and disappears from the parental MAC. Msh2 is localized in the new MAC and new MIC during the late conjugation stage. Msh2 also forms a spindle-like structure with a meiotic MIC and mitotic gametic nucleus. MSH2 knockdown inhibits the division of MAC and MIC during vegetative growth and affects cellular proliferation. MSH2 knockdown mutants are sensitive to cisplatin treatment. MSH2 knockdown also affects micronuclear meiosis and gametogenesis during sexual development. Furthermore, Msh2 interacts with MMR-dependent and MMR-independent factors. Therefore, Msh2 is necessary for macronuclear stability, as well as micronuclear mitosis and meiosis in Tetrahymena. Full article
(This article belongs to the Special Issue DNA Damage and Repair in Biology and Medicine 2.0)
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16 pages, 3719 KiB  
Article
Nuclear DJ-1 Regulates DNA Damage Repair via the Regulation of PARP1 Activity
by Zhong-Xuan Wang, Yi Liu, Yao-Lin Li, Qiao Wei, Rong-Rong Lin, Ruiqing Kang, Yang Ruan, Zhi-Hao Lin, Nai-Jia Xue, Bao-Rong Zhang and Jia-Li Pu
Int. J. Mol. Sci. 2023, 24(10), 8651; https://doi.org/10.3390/ijms24108651 - 12 May 2023
Cited by 3 | Viewed by 2195
Abstract
DNA damage and defective DNA repair are extensively linked to neurodegeneration in Parkinson’s disease (PD), but the underlying molecular mechanisms remain poorly understood. Here, we determined that the PD-associated protein DJ-1 plays an essential role in modulating DNA double-strand break (DSB) repair. Specifically, [...] Read more.
DNA damage and defective DNA repair are extensively linked to neurodegeneration in Parkinson’s disease (PD), but the underlying molecular mechanisms remain poorly understood. Here, we determined that the PD-associated protein DJ-1 plays an essential role in modulating DNA double-strand break (DSB) repair. Specifically, DJ-1 is a DNA damage response (DDR) protein that can be recruited to DNA damage sites, where it promotes DSB repair through both homologous recombination and nonhomologous end joining. Mechanistically, DJ-1 interacts directly with PARP1, a nuclear enzyme essential for genomic stability, and stimulates its enzymatic activity during DNA repair. Importantly, cells from PD patients with the DJ-1 mutation also have defective PARP1 activity and impaired repair of DSBs. In summary, our findings uncover a novel function of nuclear DJ-1 in DNA repair and genome stability maintenance, and suggest that defective DNA repair may contribute to the pathogenesis of PD linked to DJ-1 mutations. Full article
(This article belongs to the Special Issue DNA Damage and Repair in Biology and Medicine 2.0)
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