DNA Damage and Associated DNA Repair Defects in Disease and Premature Aging

Tiwari, Vinod; Wilson, David M.

doi:10.1016/j.ajhg.2019.06.005

Cited by 185 publications

(106 citation statements)

References 200 publications

(218 reference statements)

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“…DNA damage can be the result of external factors such as ionizing and ultraviolet radiation, cytotoxic or internal factors, which are: reactive oxygen species and DNA polymerase errors during replication [ 16 ]. The above factors may lead to single- and double-strand DNA breaks, which are identified by the TUNEL assay.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of the Anticancer Activities of Novel Transition Metal Complexes with Berenil and Nitroimidazole

et al. 2020

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Novel transition metal complexes (Au, Pd, Pt) with berenil and 2-(1-methyl-5-nitroimidazol-2-yl)ethanol were obtained through two-step synthesis. The cytotoxicity assay against MCF-7 and MDA-MB-231 breast cancer cells revealed that novel platinum and palladium complexes cause a reduction on the viability of MCF-7 and MDA-MB-231 breast cancer cells to a greater extent than cisplatin. The complexes showed lower cytotoxicity on normal MCF-10A human breast epithelial cells than on tumor cells. Furthermore, we observed that these complexes selectively concentrate in tumor cell mitochondria due to the characteristic for these cells increased membrane potential that may explain their increased proapoptotic activity. The activity of the synthesized compounds against topoisomerase type IIα and their increased impact on DNA defragmentation also were documented. The novel complexes also induced autophagosome changes and inhibited tumor growth in xenograft models (established using breast cancer cells).

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Section: Resultsmentioning

confidence: 99%

Evaluation of the Anticancer Activities of Novel Transition Metal Complexes with Berenil and Nitroimidazole

et al. 2020

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“…In fact, DNA repair, DNA damage tolerance and DDR pathways are disrupted or deregulated in many cancers, thus the increases of mutagenesis and genomic instability is often addressed as the cause of cancer progression [ 19 , 20 , 43 ]. In the same way, aging is attributed to the wear and tear of chromosomal ends and failing capacities of a combination of these pathways to prove the errors [ 44 , 45 ]. Furthermore, neurodegenerative disorders also seem to be the result of a combinatorial failure of more than one of these processes [ 46 , 47 ].…”

Section: Dna Damage and Dna Damage Responsementioning

confidence: 99%

DNA Damage Response and Immune Defense

Nastasi

Mannarino

D’Incalci

2020

IJMS

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DNA damage is the cause of numerous human pathologies including cancer, premature aging, and chronic inflammatory conditions. The DNA damage response (DDR), in turn, coordinates DNA damage checkpoint activation and promotes the removal of DNA lesions. In recent years, several studies have shown how the DDR and the immune system are tightly connected, revealing an important crosstalk between the two of them. This interesting interplay has opened up new perspectives in clinical studies for immunological diseases as well as for cancer treatment. In this review, we provide an overview, from cellular to molecular pathways, on how DDR and the immune system communicate and share the crucial commitment of maintaining the genomic fitness.

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“…In addition, reliable DNA protection is one of the reasons for the immortality of germline cells [ 17 ]. Genome instability accompanies age-related diseases such as cancer, heart failure, type 2 diabetes, chronic obstructive pulmonary disease, stroke, Alzheimer’s disease and Parkinson’s disease, chronic kidney disease, atherosclerosis, osteoporosis, sarcopenia [ 7 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

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Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.

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DNA Damage and Associated DNA Repair Defects in Disease and Premature Aging

Cited by 185 publications

References 200 publications

Evaluation of the Anticancer Activities of Novel Transition Metal Complexes with Berenil and Nitroimidazole

Evaluation of the Anticancer Activities of Novel Transition Metal Complexes with Berenil and Nitroimidazole

DNA Damage Response and Immune Defense

Genome-Protecting Compounds as Potential Geroprotectors

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