Review
Cell Biology
Ksenia G. Kolobynina, Alexander Rapp, M. Cristina Cardoso
Summary: Chromatin serves as the background for all DNA-based molecular processes in the cell nucleus. The initial chromatin structure at the site of DNA damage determines lesion generation and activation of the DNA damage response pathway. Ubiquitination, as an important chromatin post-translational modification, is involved in chromatin changes at the damaged site and throughout the genome.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Environmental Sciences
Ericka Marel Quezada-Maldonado, Yesennia Sanchez-Perez, Yolanda I. Chirino, Claudia M. Garcia-Cuellar
Summary: This study analyzed the types of DNA damage and alterations in DNA repair pathways induced by PM exposure, showing that PM mainly causes oxidative stress and DNA damage through the formation of DNA adducts and DSBs, as well as deregulates the protein expression in DNA repair pathways. However, there are still limitations in the knowledge about the effects of PM on DNA repair pathways, and further research is needed to deepen our understanding.
ENVIRONMENTAL POLLUTION
(2021)
Article
Multidisciplinary Sciences
Michael Schmalz, Xiao- Xuan Liang, Ines Wieser, Caroline Gruschel, Lukas Muskalla, Martin Thomas Stoeckl, Roland Nitschke, Norbert Linz, Alfred Leitenstorfer, Alfred Vogel, Elisa Ferrando-May, Wei Yang
Summary: Understanding and predicting the outcome of light-DNA interaction is crucial for DNA repair and radiotherapy. This study combines laser microirradiation, imaging, and modeling to investigate the damage pathways in live cells. The results show that photochemical damage dominates at 515 nm, while electron-mediated damage dominates at wavelengths ≥620 nm. The study provides a conceptual framework for interpreting the wavelength-dependent DNA damage induced by laser and electron interactions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Philipp Palombo, Alexander Buerkle, Maria Moreno-Villanueva
Summary: In vitro mechanistic research often overlooks the potential influence of cell culture media and supplements, leading to the potential oversight of interactions between compounds and medium ingredients. Isoproterenol, a synthetic catecholamine commonly used in biomedical research, has different stability in different cell culture media. The differences in effective levels of isoproterenol and the formation of oxidation products may explain the discrepancies observed in its genotoxicity and cytotoxicity.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Review
Genetics & Heredity
Apfrida Kendek, Marieke R. Wensveen, Aniek Janssen
Summary: The eukaryotic nucleus is constantly exposed to sources causing DNA breaks, requiring dedicated nuclear machinery for faithful repair. DNA is packaged into various chromatin domains with specific molecular properties regulating gene expression and nuclear structure maintenance. Different chromatin environments demand tailored responses to DNA damage.
Article
Cell Biology
Nathalie Berthault, Ptissam Bergam, Floriane Pereira, Pierre-Marie Girard, Marie Dutreix
Summary: AsiDNA, a DNA repair inhibitor, disrupts DNA double-strand breaks (DSB) repair pathways to sensitize tumors to DNA damaging therapies. It activates ATM and PARP in the cytoplasm, preventing the formation of repair foci on irradiation-induced damage. AsiDNA also associates with DNA-PK in the nucleus to inhibit the recruitment of repair enzymes at damage sites.
Article
Biochemistry & Molecular Biology
Dimitra T. Stefanou, Marousa Kouvela, Dimitris Stellas, Konstantinos Voutetakis, Olga Papadodima, Konstantinos Syrigos, Vassilis L. Souliotis
Summary: The deregulated DNA damage response network is associated with the onset and progression of lung cancer. This study found that lung cancer patients have higher levels of endogenous DNA damage, which may be caused by oxidative stress and defective DNA repair mechanisms. The findings suggest that oxidative stress and DDR-related aberrations contribute to the accumulation of endogenous DNA damage in lung cancer patients.
Article
Cell Biology
Xiaoqing Li, Dexuan Gao, Fei Shen, Hengrui Chen, Zhuqiang Zhang, Chao He, Aidi Gao, Yue Lang, Xiaozhong Zhu, Jundong Zhou, Zeng-Fu Shang, Wei-Qun Ding, Ji Zhu
Summary: Radiotherapy resistance is a crucial challenge in managing esophageal squamous carcinoma (ESCC), but the factors and molecular mechanisms underlying ESCC resistance to radiotherapy are not fully understood. This study found that high expression of DNA polymerase iota (POLI) is associated with shorter survival in ESCC patients receiving radiotherapy. Down-regulating POLI increased ESCC sensitivity to radiation and prolonged DNA damage markers. POLI stabilizes RAD51 protein by competitively binding with E3 ligase XIAP and blocking RAD51's ubiquitination, leading to the activation of the GAS signaling pathway. These findings provide new insights into the role of POLI in ESCC radioresistance by stabilizing RAD51 protein.
CELL DEATH DISCOVERY
(2023)
Article
Immunology
Maria Pappa, Panagiotis A. Ntouros, Christina Papanikolaou, Petros P. Sfikakis, Vassilis L. Souliotis, Maria G. Tektonidou
Summary: Antiphospholipid syndrome (APS) is a rare autoimmune disorder characterized by oxidative stress and decreased DNA repair mechanisms, leading to the accumulation of endogenous DNA damage. In this study, thrombotic primary APS (thrPAPS) patients showed significantly higher levels of endogenous DNA damage, increased oxidative stress, and abasic sites, as well as lower nucleotide excision repair (NER) and double-strand breaks repair (DSB/R) capacities compared to healthy controls and asymptomatic antiphospholipid antibody (aPL) positive individuals without APS. These findings suggest that oxidative stress and impaired DNA repair may serve as potential therapeutic targets and biomarkers for APS.
CLINICAL IMMUNOLOGY
(2023)
Article
Geriatrics & Gerontology
Evrydiki Kravvariti, Panagiotis A. Ntouros, Nikolaos Vlachogiannis, Maria Pappa, Vassilis L. Souliotis, Petros P. Sfikakis
Summary: Defects in the DNA damage response and repair network accumulate during aging, leading to physical frailty. This study found that older individuals had increased levels of oxidative stress and DNA damage, as well as reduced DNA repair capacity, compared to younger controls. These abnormalities were more pronounced in frail older adults and were associated with individual frailty levels, suggesting their potential as biomarkers for frailty.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Genevieve Trombly, Afaf Milad Said, Alexei P. Kudin, Viktoriya Peeva, Janine Altmueller, Kerstin Becker, Karl Koehrer, Gabor Zsurka, Wolfram S. Kunz
Summary: The study investigated the effects of hydrogen peroxide on mitochondrial DNA integrity. The results showed that hydrogen peroxide treatment resulted in DNA breaks, which were then repaired through rapid repair of single-strand breaks and degradation of double-strand breaks-generated linear fragments. Inactivation of mitochondrial DNA degradation resulted in the persistence of linear fragments in mutant cells without affecting the repair of single-strand breaks. These findings highlight the interplay between DNA repair and degradation processes, and the potential generation of somatic mitochondrial DNA deletions.
Review
Cell Biology
Marcelo Santos da Silva
Summary: This article discusses the unique dependence of trypanosomatids on DSBs for important events such as antigenic variation, genetic exchange, and genomic changes, as well as how they balance the benefits and challenges caused by DSBs through homologous recombination.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ricardo Peraza-Vega, Mahara Valverde, Emilio Rojas
Summary: The repair of DNA damage is crucial for maintaining genetic information and cell functioning. Double-strand breaks (DSBs) are the most harmful type of DNA damage, and their repair involves two main mechanisms: non-homologous end joining (NHEJ) and homologous recombination repair (HRR). MiRNAs have been shown to play an important role in regulating genes involved in NHEJ and HRR, and alterations in miRNA expression can impact the ability of cells to repair DSBs and affect cancer therapy sensitivity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Kevin M. Wernke, Alina Tirla, Mengzhao Xue, Yulia Surovtseva, Fabian S. Menges, Seth B. Herzon
Summary: Colibactin is a genotoxic metabolite produced by commensal-pathogenic members of the human microbiome, potentially linked to tumorigenesis. Researchers synthesized and studied colibactin 742 (4), finding that it induces DNA interstrand-cross-links and activates DNA repair pathways, providing a new approach to study the genotoxic effects of colibactin.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Diana Rubio-Contreras, Fernando Gomez-Herreros
Summary: This study reveals that double strand breaks (DSBs) induced by DNA topoisomerase I (TOP1) can lead to genome rearrangements, which are repaired by tyrosyl-DNA phosphodiesterase 1 (TDP1), thereby protecting gene transcription and genome stability.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Angela Dziedzic, Rafal Szelenberger, Michal Kacprzak, Piotr Czarny, Ewelina Synowiec, Joanna Saluk-Bijak, Tomasz Sliwinski, Marzenna Zielinska, Michal Bijak
Summary: The pathophysiology of atherosclerosis and acute coronary syndrome (ACS) is related to interactions between immune cells, endothelium, and blood platelets. Excessive immune activation and ACS incidence are linked, and augmented expression of pro-inflammatory genes from peripheral blood cells may be a crucial genetic factor in ACS pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Marcin Kosmalski, Sylwia Ziolkowska, Piotr Czarny, Janusz Szemraj, Tadeusz Pietras
Summary: NAFLD and T2DM are closely related, with common risk factors and pathogenesis. Understanding the coexistence of NAFLD and T2DM can help prevent the occurrence of other diseases and improve quality of life.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Katarzyna Bialek, Piotr Czarny, Paulina Wigner, Ewelina Synowiec, Lukasz Kolodziej, Michal Bijak, Janusz Szemraj, Mariusz Papp, Tomasz Sliwinski
Summary: The study suggests that both chronic mild stress and agomelatine treatment can influence the expression and methylation status of certain genes in both peripheral blood and the brain, indicating their potential association with depression and its treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Izabela Szymczak-Pajor, Jozef Drzewoski, Ewa Swiderska, Justyna Strycharz, Anna Gabryanczyk, Jacek Kasznicki, Marta Bogdanska, Agnieszka Sliwinska
Summary: Accumulating evidence suggests that metformin has anticancer properties by inducing apoptosis and inhibiting the growth and proliferation of cancer cells. However, its effect on histone acetylation status remains unclear. Therefore, this study aimed to evaluate the impact of metformin on HATs and HDACs in human pancreatic cancer cell lines.
Review
Biochemistry & Molecular Biology
Malgorzata Kozlowska, Agnieszka Sliwinska
Summary: Despite medical advances, pancreatic cancer remains difficult to diagnose and has a poor prognosis. The lack of symptoms and diagnostic markers hinder accurate diagnosis. Recent studies focus on microRNAs as potential factors in pancreatic cancer development. Dysregulated microRNAs in diabetes also contribute to pancreatic cancer progression. Promising biomarkers for early detection and therapeutic microRNAs have been identified.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Edyta Janik-Karpinska, Michal Ceremuga, Marcin Niemcewicz, Ewelina Synowiec, Tomasz Sliwinski, Michal Bijak
Summary: T-2 toxin has adverse effects on Hs68 cell mitochondria, causing mitochondrial dysfunction and mtDNA damage, which can result in cell death.
Article
Genetics & Heredity
Malgorzata Drzewiecka, Anna Gajos-Michniewicz, Grazyna Hoser, Dominika Jasniak, Gabriela Barszczewska-Pietraszek, Przemyslaw Sitarek, Piotr Czarny, Janusz Piekarski, Maciej Radek, Malgorzata Czyz, Tomasz Skorski, Tomasz Sliwinski
Summary: Inhibition of HDACs shows potential as an anti-cancer therapy due to its disruption of acetylation in cancer cells. This study demonstrates that the combination of HDAC inhibitors, alkylating agents, and PARP inhibitors enhances the treatment of melanoma by increasing DNA double strand breaks and reducing cell survival. The findings suggest that HDACs play a role in melanoma cell resistance to methylating agent-based therapies.
Review
Biochemistry & Molecular Biology
Marcin Kosmalski, Agnieszka Sliwinska, Jozef Drzewoski
Summary: In clinical practice, patients often present both non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). The etiopathogenesis of NAFLD is linked to insulin resistance (IR) and obesity, while T2DM develops concurrently. Studies have not fully elucidated the mechanisms of their coexistence, making it difficult to determine which disease appears first. However, it is crucial to bring attention to the coexistence of NAFLD and T2DM to prevent their consequences.
Article
Biochemistry & Molecular Biology
Sylwia Ziolkowska, Marcin Kosmalski, Lukasz Kolodziej, Aleksandra Jablkowska, Janusz Zbigniew Szemraj, Tadeusz Pietras, Maciej Jablkowski, Piotr Lech Czarny
Summary: Oxidative stress is crucial in the development of NAFLD and can cause DNA damage. The study examined the relationship between different genetic variants of BER-associated genes and the risk of NAFLD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Edyta Janik-Karpinska, Michal Ceremuga, Marcin Niemcewicz, Ewelina Synowiec, Tomasz Sliwinski, Maksymilian Stela, Michal Bijak
Summary: This study demonstrates that T-2 toxin has genotoxic effects on human skin fibroblast cells, potentially causing damage to nuclear DNA and leading to changes in gene expression related to inflammation and repair processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Marcin Kosmalski, Izabela Szymczak-Pajor, Jozef Drzewoski, Agnieszka Sliwinska
Summary: This study investigated the association between CAT levels and -262 C/T polymorphism in the promoter of CAT (rs1001179) with NAFLD. The results showed that CAT levels were decreased in NAFLD patients and the CT genotype and T allele of -262 C/T CAT polymorphism may elevate the risk of NAFLD.
Article
Health Care Sciences & Services
Malgorzata Drzewiecka, Dominika Jasniak, Gabriela Barszczewska-Pietraszek, Piotr Czarny, Anna Kobrzycka, Marek Wieczorek, Maciej Radek, Janusz Szemraj, Tomasz Skorski, Tomasz Sliwinski
Summary: This study demonstrates the potential of combining HDAC inhibitors with PARP1 inhibitors in inducing DNA damage and reducing glioblastoma. This combination therapy holds important implications for the treatment of glioblastoma, the most aggressive type of brain cancer.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Piotr Czarny, Sylwia Ziolkowska, Lukasz Kolodziej, Cezary Watala, Paulina Wigner-Jeziorska, Katarzyna Blizniewska-Kowalska, Katarzyna Wachowska, Malgorzata Galecka, Ewelina Synowiec, Piotr Galecki, Michal Bijak, Janusz Szemraj, Tomasz Sliwinski
Summary: This study explores the impact of SNPs in genes encoding enzymes involved in mtDNA replication, repair, or degradation on the occurrence, onset, severity, and treatment of MDD. The findings suggest that mtDNA damage and impairment in its metabolism play a crucial role in the development and treatment of depression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
