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Werner Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Genomic instability represents one of the key mechanisms (the others being telomere attrition, epigenetic alterations [e.g., DNA methylation], loss of proteostasis, deregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication) that underline the aging process as well as cancer susceptibility. DNA repair machinery and telomeres play a crucial role in ensuring genome integrity and stability. Functioning as DNA-dependent ATPase and ATP-dependent DNA unwinding enzyme, RecQ helicase protects genome stability by regulating DNA repair pathways and telomeres. Mutations in RecQ helicase-encoding genes have serious consequences [8–10].
Genomic Instability During Aging of Postmitotic Mammalian Cells
Published in Alvaro Macieira-Coelho, Molecular Basis of Aging, 2017
Genetic instability, genomic instability, and chromosomal instability are terms that have been used somewhat interchangeably, although they tend to have different connotations. In this review, chromosomal instability will be used to describe visible changes in the nucleoprotein complexes that constitute the characteristic structure of individual mitotic chromosomes, i.e., a change in the individual cell’s normal karyotype. Genetic instability will be used to discuss changes in the primary structure of DNA, including covalent modifications (damage) and replication-dependent events (mutations). Lastly, genomic instability will be used to describe all changes that affect DNA-based information in a cell, encompassing both chromosomal and genetic instability, in addition to epigenetic changes. In a final section, the effects of aging on the stability of mitochondrial genomes will be examined. To conclude, there will be an attempt to summarize the evidence that genomic instability is a primary aging process, to determine if sets of data define age-related patterns, to see if predictions can be made from such patterns, and to outline attractive candidates for future study or experimental strategies that might yield more meaningful results.
Introductory Remarks
Published in Dongyou Liu, Tumors and Cancers, 2017
In essence, tumorigenesis is a cumulative process that demonstrates several notable hallmarks, including (i) sustaining proliferative signaling, (ii) activating local invasion and metastasis, (iii) resisting apoptosis and enabling replicative immortality, (iv) inducing angiogenesis and inflammation, (v) evading immune destruction, (vi) deregulating cellular energetics, and (vii) genome instability and mutation.
Approaches for the setting of occupational exposure limits (OELs) for carcinogens
Published in Critical Reviews in Toxicology, 2023
Genomic instability (the increased tendency for mutations to occur during various types of cellular stress) leading to permanent genetic alterations may be common for many cancer types (Tubbs and Nussenzweig 2017), and efforts to characterise its importance in mathematical terms for the carcinogenesis of e.g. human lung cancer and colon cancer induced by radiation and other external factors have been presented (Kaiser et al. 2014; Li et al. 2019). Genomic instability may lead to hundreds of mutations. A role in experimental chemical carcinogenesis has been indicated (Liu et al. 2015). These examples challenge the concept that a certain order of 6–7 mutations explains the exponential increase of cancer with age, as suggested by Armitage and Doll (1954) and Nordling (1953) (Section 2.5).
Effects of genomic instability in populations of Drosophila melanogaster from regions of Ukraine with different impact of radiation factors
Published in International Journal of Radiation Biology, 2023
Alexandra Kravets, Daryna Sokolova
Genetic and radiobiological studies of the last decades have shown that the most important effect of radiation exposure with low intensity is the emergence of genomic instability and its transmission through generations. Forms of manifestation and distant consequences of genomic instability are equally diverse (structural reorganization of the genome, activation of mobile elements, developmental violations, including fluctuating asymmetry, oncological diseases) as well as difficult to predict (Pelevina et al. 1996; Leung et al. 2000; Kuzmina and Suskov 2002; Suskov and Kuzmina 2003; Angelopoulou et al. 2009; Dancause et al. 2010; De Toledo et al. 2017; Fang et al. 2019; Siama et al. 2019). This phenomenon is investigated in various experimental models and has already been identified by some key features: the possibility of transgenerational transmission, the non-clonality of genome disorders that is the instability of the reaction, which is determined by many components.
The sine qua non of the fish invitrome today and tomorrow in environmental radiobiology
Published in International Journal of Radiation Biology, 2022
Genomic instability refers to an increase in mutation loads and varied phenotypic expressions after subsequent generations. Delayed lethal mutations can develop as a result of genomic instability, which can lead to the diminishment of stem cell pools in the body and embryonic lethality. Genomic instability and delayed lethal mutations have been previously demonstrated in animals both kept in the laboratory and sampled in the wild (Shimada and Shima 2004; Hurem et al. 2018; Kamstra et al. 2018; Hancock et al. 2019a, 2019b, 2020). This concept can be conveniently demonstrated with fish cell lines. Recent demonstrations were with CHSE-214 and eelB cell lines following chronic low dose alpha and acute gamma irradiations (Shi et al. 2016b, 2018; Vo et al. 2017b, 2019b). Chronic irradiation with environmentally relevant doses of alpha-emitting Ra-226 induces genomic instability and delayed lethal mutations in CHSE-214 salmon embryonic cells (Shi et al. 2018). Acute gamma irradiation induces genomic instability and delayed lethal mutations in eelB brain endothelial cells but not in CHSE-214 cells (Vo et al. 2017b, 2019b; Shi et al. 2018). Inheritance of radiation-induced DNA methylation patterns from radiation parental survivors is strongly linked to genomic instability in fish (Kamstra et al. 2018). Studying DNA methylation mechanisms with fish cell lines is both convenient and high throughput.