Introduction to Genomics
Altuna Akalin in Computational Genomics with R, 2020
Mutations in the genome occur due to multiple reasons. First, DNA replication is not an error-free process. Before a cell division, the DNA is replicated with 1 mistake per 10^8 to 10^10 base-pairs. Second, mutagens such as UV light can induce mutations on the genome. The third factor that contributes to mutation is imperfect DNA repair. Every day, any human cell suffers multiple instances of DNA damage. DNA repair enzymes are there to cope with this damage but they are also not error-free, depending on which DNA repair mechanism is used (there are multiple), mistakes will be made at varying rates.
Causes Of Alzheimer’s Disease
Zaven S. Khachaturian, Teresa S. Radebaugh in Alzheimer’s Disease, 2019
Considerable heterogeneity has already been identified in the susceptibility of individuals to toxins. Individuals have different kinds and amounts of liver enzymes to detoxify exogenous and endogenous toxins. Just as genetic mutations can lead to disease, normal genetic variation can lead to disease susceptiblity. Some of the best examples of this is susceptibility to cancer. DNA repair enzymes differ in their properties. If an individual is never under undue stress, no consequences of the genetic differences are apparent. If, however, the individuals are exposed to toxins, then those whose repair enzymes are not as active or efficient as others have a higher incidence of certain kinds of cancer such as colon cancer. Investigators are now looking furiously for such factors in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Variants for the gene for ApoE, for instance, appear to confer different degrees of susceptibility to Alzheimer’s disease.12 Whether this susceptibility arises from a differential sensitivity to an endogenous toxin is as yet unknown but it is certainly a likely possibility.
(-)-Epigallocatechin gallate from green tea increases the level of a DNA repair enzyme
Elida Zairina, Junaidi Khotib, Chrismawan Ardianto, Syed Azhar Syed Sulaiman, Charles D. Sands, Timothy E. Welty in Unity in Diversity and the Standardisation of Clinical Pharmacy Services, 2017
The development of drugs from natural ingredients to prevent or treat cancer has now reached the molecular level. The ability to prevent cancer risk is closely related to the ability to repair DNA damage. Various pollutants and carcinogenic compounds attack the DNA and produce cancer cells. Cancer can be avoided if this DNA damage is prevented. One strategy of cancer treatment is to search compounds or extracts that are able to protect DNA from damage that causes mutations. Research using green tea major component (-)-epigallocatechin gallate (EGCG) has proved that there is a significant relationship between EGCG levels and DNA repair (Efimova et al., 2016). Increasing the activity of DNA repair enzymes in cells is an important step to prevent DNA damage, thereby preventing tumors and cancer. It has been shown that administration of 45.34% theaflavin or 28.32% EGCG prevents DNA damage induced by 7,12-dimethylbenz(a)anthracene (DMBA). This suggests that EGCG has the ability to protect cells from DNA damage (Srivastava et al. 2013). Therefore, EGCG from green tea has a high potential to be developed into a compound that provides protection against tumors and cancer.
Ponatinib is a potential therapeutic approach for malignant pleural mesothelioma
Published in Experimental Lung Research, 2021
Yi-Wei Yang, Angelica Marrufo, Jillian Chase, Gavitt A. Woodard, David M. Jablons, Hassan Lemjabbar-Alaoui
DNA repair enzymes are critical for maintaining the genome,32 and defects in the repair process lead to genome instability and promote tumorigenesis.33,34 Conversely, good DNA repair provides resistance to therapeutic radiation and some cytotoxic chemotherapy.26 Moreover, combined impairment in different DNA repair systems results in gross genomic instability and death of tumor cells, a principle called “synthetic lethality.”35,36 Radiation therapy, as well as the majority of chemotherapy, weaken cancer cells by damaging DNA. Successful DNA repair is essential for the normal cells to surmount the therapy's adverse effects, but in the tumor can result in treatment resistance. cAbl inhibition has been recently shown to alter DNA damage response.30 DNA damage elicits cAbl activation, which then binds and activates DNA damage repair proteins, including ATM, ATR, Rad51, BRCA1, DNA-PK, RFX1, and p73.23 Moreover, activated cAbl increases the Rad51 gene.
Influence of extremely low-frequency magnetic field on chemotherapy and electrochemotherapy efficacy in human Caco-2 colon cancer cells
Published in Electromagnetic Biology and Medicine, 2022
Mehmet Esref Alkis, Mehmet Zulkuf Akdag, Sevgi Irtegun Kandemir
In general, the present study revealed that the ELF-MF exposure before and after CT and ECT caused an increase in the cell viability compared to the treatments without ELF-MF. Our results suggest that ELF-MF exposure may cause a protective response. This may be explained by that the ELF-EMF exposure may produce a “triggering effect” that does not cause a significant increase in the genetic damage but stimulates the signal transduction pathways, resulting in the activation of cell defense mechanism and consequently providing protection from the genotoxic agent subsequently applied (Mansourian et al. 2020). The triggered cell defense may enable the cells to show a resistance against the high-level damage caused by ECT and CT. Resistance to ECT/CT might also be due to the ELF-MF-induced DNA repair. This resistance might develop in many ways. The change in cytosolic ion concentration (especially Ca++) significantly affects DNA repair, and this change might be caused by EMF (Blackman et al. 1980; Gafter et al. 1997; Mansourian et al. 2020). DNA repair enzymes fix the damage to the DNA molecules, caused by x- and gamma rays, endogenous ROS, plant toxins, ultraviolet radiation, mutagenic chemicals, and CT drugs. DNA repair is classified in two types: nucleotide excision repair and base excision repair, which can confer the resistance to chemo agents targeting DNA (Zheng 2017).
Genetic polymorphisms in DNA repair genes and their association with cervical cancer
Published in British Journal of Biomedical Science, 2019
M Abbas, K Srivastava, M Imran, M Banerjee
DNA-repair systems are necessary for the maintenance of genetic integrity, dysfunction of which will lead to the development of cancer [18]. There are different types of DNA repair system viz. Base-Excision Repair (BER) pathway for single strand breaks (SSBs) and Nucleotide Excision Repair (NER) system for double-strand DNA breaks (DSBs). Principle mechanisms of repair systems are homologous recombination (HR) and non-homologous end joining (NHEJ) [19]. X-ray cross-complementing group 1 (XRCC1) is BER protein that may play an important role to prevent DNA from damaging agents [20]. The important molecules of HRR pathway are RAD51, XRCC2 and XRCC3 [21]. Repair of DSBs is an important component of these genes. Structure and function of XRCC2 and XRCC3 genes are related to the RAD51 gene. RAD51 functional defect results in an increased mutation rate that lead to accumulation of DNA damage and subsequently increased cancer risk [22].