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Biochimica Et Biophysica Acta. Reviews... Sep 2023Mitotic catastrophe is distinct from other cell death modes due to unique nuclear alterations characterized as multi and/or micronucleation. Mitotic catastrophe is a... (Review)
Review
Mitotic catastrophe is distinct from other cell death modes due to unique nuclear alterations characterized as multi and/or micronucleation. Mitotic catastrophe is a common and virtually unavoidable consequence during cancer therapy. However, a comprehensive understanding of mitotic catastrophe remains lacking. Herein, we summarize the anticancer drugs that induce mitotic catastrophe, including microtubule-targeting agents, spindle assembly checkpoint kinase inhibitors, DNA damage agents and DNA damage response inhibitors. Based on the relationships between mitotic catastrophe and other cell death modes, we thoroughly evaluated the roles played by mitotic catastrophe in cancer treatment as well as its advantages and disadvantages. Some strategies for overcoming its shortcomings while fully utilizing its advantages are summarized and proposed in this review. We also review how mitotic catastrophe regulates cancer immunotherapy. These summarized findings suggest that the induction of mitotic catastrophe can serve as a promising new therapeutic approach for overcoming apoptosis resistance and strengthening cancer immunotherapy.
Topics: Humans; Neoplasms; Cell Death; Immunotherapy; Apoptosis; DNA Damage
PubMed: 37625527
DOI: 10.1016/j.bbcan.2023.188965 -
Toxins Oct 2023is a common species of red tide dinoflagellate that causes the mass mortality of marine fauna in coastal waters of Republic of Korea. Despite continuous studies on the...
is a common species of red tide dinoflagellate that causes the mass mortality of marine fauna in coastal waters of Republic of Korea. Despite continuous studies on the ecophysiology and toxicity of , the underlying molecular mechanisms remain poorly understood. Red sea bream, is a high-value aquaculture fish species, and the coastal aquaculture industry of red sea bream has been increasingly affected by red tides. To investigate the potential oxidative effects of on and the molecular mechanisms involved, we exposed the fish to varying concentrations of and evaluated its toxicity. Our results showed that exposure to led to an accumulation of reactive oxygen species (ROS) and oxidative DNA damage in the gill tissue of . Furthermore, we found that induced the activation of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, in the gill tissue of , with a significant increase in activity at concentrations above 5000 cells/mL. However, the activity of glutathione -transferase did not significantly increase at the equivalent concentration. Our study confirms that oxidative stress and DNA damage is induced by acute exposure to as it produces ROS and hypoxic conditions in . In addition, it was confirmed that gill and blood samples can be used as biomarkers to detect the degree of oxidative stress in fish. These findings have important implications for the aquaculture of red sea bream, particularly in the face of red tide disasters.
Topics: Animals; Dinoflagellida; Reactive Oxygen Species; Harmful Algal Bloom; Perciformes; Oxidative Stress; DNA Damage
PubMed: 37888651
DOI: 10.3390/toxins15100620 -
Journal of Translational Medicine Sep 2023Genomic instability is a common hallmark of human tumours. As a carrier of genetic information, DNA is constantly threatened by various damaging factors that, if not... (Review)
Review
Genomic instability is a common hallmark of human tumours. As a carrier of genetic information, DNA is constantly threatened by various damaging factors that, if not repaired in time, can affect the transmission of genetic information and lead to cellular carcinogenesis. In response to these threats, cells have evolved a range of DNA damage response mechanisms, including DNA damage repair, to maintain genomic stability. The X-ray repair cross-complementary gene family (XRCC) comprises an important class of DNA damage repair genes that encode proteins that play important roles in DNA single-strand breakage and DNA base damage repair. The dysfunction of the XRCC gene family is associated with the development of various tumours. In the context of tumours, mutations in XRCC and its aberrant expression, result in abnormal DNA damage repair, thus contributing to the malignant progression of tumour cells. In this review, we summarise the significant roles played by XRCC in diverse tumour types. In addition, we discuss the correlation between the XRCC family members and tumour therapeutic sensitivity.
Topics: Humans; X-Rays; Neoplasms; DNA Repair; Carcinogenesis; DNA Damage
PubMed: 37679817
DOI: 10.1186/s12967-023-04447-2 -
Scientific Reports Oct 2023To further explore the pharmacological effect of pachymaran, this article studied the inhibition of pachymaran on oxidative stress and genetic damage induced by...
To further explore the pharmacological effect of pachymaran, this article studied the inhibition of pachymaran on oxidative stress and genetic damage induced by formaldehyde. 40 adult Kunming male mice were randomly divided into four groups with different interventions. One week later, the contents of serum SOD, GR, MDA, DNA-protein crosslink (DPC), 8-hydroxydeoxyguanosine (8-OHDG) and DNA adduct were determined by ELISA. The results showed that there were statistically significant differences in the contents of SOD, GR and MDA among the four groups (P < 0.01). The activity of SOD and GR increased along with the increase of pachymaran dosage (SOD: r = 0.912, P < 0.01; GR: r = 0.857, P < 0.01), while the content of MDA showing a significant negative correlation (r = - 0.893, P < 0.01). There were statistically significant differences in the levels of DPC, 8-OHDG and DNA adduct among the four groups (DPC and DNA adduct: P < 0.01, 8-OHDG: P < 0.05), the concentration decreased along with the increase of pachymaran dosage (DPC: r = - 0.855, P < 0.01; 8-OHDG:r = - 0.412, P < 0.05, DNA adduct: γ = - 0.869, P < 0.01). It can be inferred that pachymaran can inhibit oxidative stress and DNA damage induced by formaldehyde with the dose-effect relationship.
Topics: Mice; Animals; Male; DNA Adducts; 8-Hydroxy-2'-Deoxyguanosine; DNA Damage; Oxidative Stress; Formaldehyde; Proteins; Superoxide Dismutase; Deoxyguanosine
PubMed: 37838763
DOI: 10.1038/s41598-023-44788-y -
Experimental Dermatology Sep 2023Far-UVC radiation sources of wavelengths 222 nm and 233 nm represent an interesting potential alternative for the antiseptic treatment of the skin due to their high...
Far-UVC radiation sources of wavelengths 222 nm and 233 nm represent an interesting potential alternative for the antiseptic treatment of the skin due to their high skin compatibility. Nevertheless, no studies on far-UVC-induced DNA damage in different skin types have been published to date, which this study aims for. After irradiating the skin with far-UVC of the wavelengths 222 and 233 nm as well as broadband UVB, the tissue was screened for cyclobutane pyrimidine dimer-positive (CPD ) cells using immunohistochemistry. The epidermal DNA damage was lower in dark skin types than in fair skin types after irradiation at 233 nm. Contrary to this, irradiation at 222 nm caused no skin type-dependent differences, which can be attributed to the decreased penetration depth of radiation. UVB showed the relatively strongest differences between light and dark skin types when using a suberythemal dose of 3 mJ/cm . As melanin is known for its photoprotective effect, we evaluated the ratio of melanin content in the stratum basale and stratum granulosum in samples of different skin types using two-photon excited fluorescence lifetime imaging (TPE-FLIM) finding a higher ratio up to skin type IV-V. As far-UVC is known to penetrate only into the upper layers of the viable skin, the aforementioned melanin ratio could explain the less pronounced differences between skin types after irradiation with far-UVC compared to UVB.
Topics: Melanins; DNA Damage; Pyrimidine Dimers; Epidermis; Ultraviolet Rays
PubMed: 37545424
DOI: 10.1111/exd.14902 -
Molecular Cell Apr 2024Micronuclei (MN) are induced by various genotoxic stressors and amass nuclear- and cytoplasmic-resident proteins, priming the cell for MN-driven signaling cascades....
Micronuclei (MN) are induced by various genotoxic stressors and amass nuclear- and cytoplasmic-resident proteins, priming the cell for MN-driven signaling cascades. Here, we measured the proteome of micronuclear, cytoplasmic, and nuclear fractions from human cells exposed to a panel of six genotoxins, comprehensively profiling their MN protein landscape. We find that MN assemble a proteome distinct from both surrounding cytoplasm and parental nuclei, depleted of spliceosome and DNA damage repair components while enriched for a subset of the replisome. We show that the depletion of splicing machinery within transcriptionally active MN contributes to intra-MN DNA damage, a known precursor to chromothripsis. The presence of transcription machinery in MN is stress-dependent, causing a contextual induction of MN DNA damage through spliceosome deficiency. This dataset represents a unique resource detailing the global proteome of MN, guiding mechanistic studies of MN generation and MN-associated outcomes of genotoxic stress.
Topics: Humans; Proteome; Proteomics; Cell Nucleus; DNA Damage; Chromothripsis
PubMed: 38423013
DOI: 10.1016/j.molcel.2024.02.001 -
DNA Repair Sep 2023The perturbation of DNA replication, a phenomena termed "replication stress", is a driving force of genome instability and a hallmark of cancer cells. Among the DNA... (Review)
Review
The perturbation of DNA replication, a phenomena termed "replication stress", is a driving force of genome instability and a hallmark of cancer cells. Among the DNA repair mechanisms that contribute to tolerating replication stress, the homologous recombination pathway is central to the alteration of replication fork progression. In many organisms, defects in the homologous recombination machinery result in increased cell sensitivity to replication-blocking agents and a higher risk of cancer in humans. Moreover, the status of homologous recombination in cancer cells often correlates with the efficacy of anti-cancer treatment. In this review, we discuss our current understanding of the different functions of homologous recombination in fixing replication-associated DNA damage and contributing to complete genome duplication. We also examine which functions are pivotal in preventing cancer and genome instability.
Topics: Humans; DNA Replication; DNA Damage; Homologous Recombination; DNA Repair; Genomic Instability
PubMed: 37541027
DOI: 10.1016/j.dnarep.2023.103548 -
Biochemistry. Biokhimiia Nov 2023In the last ten years, the discovery of neuronal DNA postmitotic instability has changed the theoretical landscape in neuroscience and, more broadly, biology. In 2003,... (Review)
Review
In the last ten years, the discovery of neuronal DNA postmitotic instability has changed the theoretical landscape in neuroscience and, more broadly, biology. In 2003, A. M. Olovnikov suggested that neuronal DNA is the "initial substrate of aging". Recent experimental data have significantly increased the likelihood of this hypothesis. How does neuronal DNA accumulate damage and in what genome regions? What factors contribute to this process and how are they associated with aging and lifespan? These questions will be discussed in the review. In the course of Metazoan evolution, the instability of neuronal DNA has been accompanied by searching for the pathways to reduce the biological cost of brain activity. Various processes and activities, such as sleep, evolutionary increase in the number of neurons in the vertebrate brain, adult neurogenesis, distribution of neuronal activity, somatic polyploidy, and RNA editing in cephalopods, can be reconsidered in the light of the trade-off between neuronal plasticity and DNA instability in neurons. This topic is of considerable importance for both fundamental neuroscience and translational medicine.
Topics: Animals; Longevity; Neurons; Brain; DNA Damage; DNA
PubMed: 38105193
DOI: 10.1134/S0006297923110044 -
Journal of Molecular Biology Jan 2024TIMELESS protein (TIM) protects replication forks from stalling at difficult-to-replicate regions and plays an important role in DNA damage response, including... (Review)
Review
TIMELESS protein (TIM) protects replication forks from stalling at difficult-to-replicate regions and plays an important role in DNA damage response, including checkpoint signaling, protection of stalled replication forks and DNA repair. Loss of TIM causes severe replication stress, while its overexpression is common in various types of cancer, providing protection from DNA damage and resistance to chemotherapy. Although TIM has mostly been studied for its part in replication stress response, its additional roles in supporting genome stability and a wide variety of other cellular pathways are gradually coming to light. This review discusses the diverse functions of TIM and its orthologs in healthy and cancer cells, open questions, and potential future directions.
Topics: Humans; Carrier Proteins; Cell Cycle Proteins; DNA Damage; DNA Replication; DNA-Binding Proteins; Genomic Instability; Intracellular Signaling Peptides and Proteins; Nuclear Proteins
PubMed: 37481157
DOI: 10.1016/j.jmb.2023.168206 -
DNA Repair Sep 2023The human genome is continually exposed to various stressors, which can result in DNA damage, mutations, and diseases. Among the different types of DNA damage,... (Review)
Review
The human genome is continually exposed to various stressors, which can result in DNA damage, mutations, and diseases. Among the different types of DNA damage, single-strand lesions are commonly induced by external stressors and metabolic processes. Accurate detection and quantification of DNA damage are crucial for understanding repair mechanisms, assessing environmental impacts, and evaluating response to therapy. However, traditional techniques have limitations in sensitivity and the ability to detect multiple types of damage. In recent years, single-molecule fluorescence approaches have emerged as powerful tools for precisely localizing and quantifying DNA damage. Repair Assisted Damage Detection (RADD) is a single-molecule technique that employs specific repair enzymes to excise damaged bases and incorporates fluorescently labeled nucleotides to visualize the damage. This technique provides valuable insights into repair efficiency and sequence-specific damage. In this review, we discuss the principles and applications of RADD assays, highlighting their potential for enhancing our understanding of DNA damage and repair processes.
Topics: Humans; DNA Repair; DNA Damage
PubMed: 37467630
DOI: 10.1016/j.dnarep.2023.103533