scholarly journals Upregulation of DNA repair genes and cell extrusion underpin the remarkable radiation resistance of Trichoplax adhaerens

PLoS Biology ◽  
2021 ◽  
Vol 19 (11) ◽  
pp. e3001471
Author(s):  
Angelo Fortunato ◽  
Alexis Fleming ◽  
Athena Aktipis ◽  
Carlo C. Maley
Keyword(s):  
Dna Repair ◽  
Molecular Genetic ◽  
Model Organism ◽  
Tissue Level ◽  
Cancer Resistance ◽  
X Ray ◽  
Trichoplax Adhaerens ◽  
Cancer Suppression ◽  
Multicellular Organisms ◽  
Repair Genes

Trichoplax adhaerens is the simplest multicellular animal with tissue differentiation and somatic cell turnover. Like all other multicellular organisms, it should be vulnerable to cancer, yet there have been no reports of cancer in T. adhaerens or any other placozoan. We investigated the cancer resistance of T. adhaerens, discovering that they are able to tolerate high levels of radiation damage (218.6 Gy). To investigate how T. adhaerens survive levels of radiation that are lethal to other animals, we examined gene expression after the X-ray exposure, finding overexpression of genes involved in DNA repair and apoptosis including the MDM2 gene. We also discovered that T. adhaerens extrudes clusters of inviable cells after X-ray exposure. T. adhaerens is a valuable model organism for studying the molecular, genetic, and tissue-level mechanisms underlying cancer suppression.

scholarly journals Radiation resistance in Placozoa: Trichoplax adhaerens upregulates DNA repair genes and extrudes cells after exposure

2020 ◽  
Author(s):  
Angelo Fortunato ◽  
Alexis Fleming ◽  
Athena Akpitis ◽  
Carlo C. Maley
Keyword(s):  
Dna Repair ◽  
Molecular Genetic ◽  
Model Organism ◽  
Tissue Level ◽  
Cancer Resistance ◽  
X Ray ◽  
Trichoplax Adhaerens ◽  
Cancer Suppression ◽  
Multicellular Organisms ◽  
Repair Genes

AbstractTrichoplax adhaerens is the simplest multicellular animal with tissue differentiation and somatic cell turnover. Like all other multicellular organisms, it should be vulnerable to cancer, yet there have been no reports of cancer in T. adhaerens, or any other placozoan. We investigated the cancer resistance of T. adhaerens, discovering that they are able to tolerate high levels of radiation damage (240 Gy). To investigate how T. adhaerens survive levels of radiation that are lethal to other animals, we examined gene expression after the X-ray exposure, finding overexpression of genes involved in DNA repair and apoptosis including the MDM2 gene. We also discovered that T. adhaerens extrudes clusters of inviable cells after X-ray exposure. T. adhaerens is a valuable model organism for studying the molecular, genetic and tissue-level mechanisms underlying cancer suppression.

Genetic manipulation in Sulfolobus islandicus and functional analysis of DNA repair genes

2013 ◽  
Vol 41 (1) ◽  
pp. 405-410 ◽  
Author(s):  
Changyi Zhang ◽  
Bin Tian ◽  
Suming Li ◽  
Xiang Ao ◽  
Kevin Dalgaard ◽  
...  
Keyword(s):  
Dna Repair ◽  
Genetic Manipulation ◽  
Excision Repair ◽  
Model Organism ◽  
Dna Repair Genes ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
Sulfolobus Islandicus ◽  
Base Excision ◽  
Repair Genes

Recently, a novel gene-deletion method was developed for the crenarchaeal model Sulfolobus islandicus, which is a suitable tool for addressing gene essentiality in depth. Using this technique, we have investigated functions of putative DNA repair genes by constructing deletion mutants and studying their phenotype. We found that this archaeon may not encode a eukarya-type of NER (nucleotide excision repair) pathway because depleting each of the eukaryal NER homologues XPD, XPB and XPF did not impair the DNA repair capacity in their mutants. However, among seven homologous recombination proteins, including RadA, Hel308/Hjm, Rad50, Mre11, HerA, NurA and Hjc, only the Hjc nuclease is dispensable for cell viability. Sulfolobus encodes redundant BER (base excision repair) enzymes such as two uracil DNA glycosylases and two putative apurinic/apyrimidinic lyases, but inactivation of one of the redundant enzymes already impaired cell growth, highlighting their important roles in archaeal DNA repair. Systematically characterizing these mutants and generating mutants lacking two or more DNA repair genes will yield further insights into the genetic mechanisms of DNA repair in this model organism.

scholarly journals Polymorphism of DNA repair genes in bronchopulmonary pathology in workers of harmful and dangerous industries

2018 ◽  
Vol 81 (1) ◽  
pp. 49-56
Author(s):  
T.A. Andruschenko ◽  
S.V. Honcharov ◽  
L.V. Dolinchuk ◽  
V.Ye. Dosenko
Keyword(s):  
Dna Repair ◽  
Molecular Genetic ◽  
Dna Repair Genes ◽  
Risk Markers ◽  
Individual Sensitivity ◽  
Asbestos Cement ◽  
Polymerase Chain ◽  
The Individual ◽  
Mutagenic Effects ◽  
Repair Genes

Introduction. Polymorphism of DNA repair genes is actively studied in the formation of the individual sensitivity of the genome to damaging mutagenic effects. Objective of the work. To study the distribution of frequencies of alleles and genotypes of DNA repair genes: XPD (rs13181, rs799793) and ERCC1 (rs11615) in workers of asbestos-cement plants and miners to identify risk markers for bronchopulmonary pathology. Material and methods. The study included workers of asbestos-cement plants and miners (n=214). Real-time polymerase chain reaction was used to determine genotypes of XPD (rs13181, rs799793) and ERCC1 (rs11615) genes. Results. The study determined alleles and genotypes associated with the risk of developing bronchopulmonary pathology: - in the population of workers of asbestos-cement plants: XPD*Asn/Asn (rs799793), (p<0.01; χ2=6.62; OR=2,20; 95 %CI: 1,75–2,77); - in the population of miners: XPD*C (rs13181), (p<0.02; χ2=4,99; OR=1,88; 95 %CI: 1,04–3,40); XPD*CC (rs13181), (p<0,003; χ2=8.61; OR=4,29; 95 %CI: 1,41–13,37). The study also detected allele XPD*A (rs13181), which in the population of miners proved to be a marker of resistance to bronchopulmonary pathology (p<0,02; χ2=4.99; OR=0,53; 95 %CI: 0,29–0,96). Conclusions. The study has identified alleles and genotypes associated with the risk of developing bronchopulmonary pathology in the population of workers in harmful and dangerous production facilities of Ukraine. The study has determined the genotype and allele that can be used as biomarkers of resistance to the pathology of the respiratory system. Key words: molecular-genetic markers, XPD and ERCC1, bronchopulmonary pathology.

Molecular genetic analysis of the polymorphism of repair genes of double-strand breaks DNA strand breaks and repair «inconsistencies» DNA in workers of hazardous industries

2019 ◽  
Vol 1 (7) ◽  
pp. 395-399
Author(s):  
Тatyana A. Andrushchenko ◽  
Sergey V. Goncharov ◽  
Viktor Е. Dosenko ◽  
Konstantin E. Ischeikin
Keyword(s):  
Dna Repair ◽  
Respiratory System ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Double Strand Breaks ◽  
Dna Repair Genes ◽  
Dna Breaks ◽  
Strand Breaks ◽  
Increased Risk ◽  
Repair Genes

Introduction. Presents results of a study of polymorphisms of repair genes of double-strand breaks DNA breaks: XRCC7 (rs7003908), ATM (rs664677), repair «inconsistencies» DNA MLH1 (rs1799977) in miners and workers of asbestos factories professionally due to broncho-pulmonary pathology. T e aim of the study was to research the frequency distribution of genotypes of DNA repair genes: XRCC7 (rs7003908), ATM (rs664677) and MLH1 (rs1799977) in workers of harmful and dangerous industries to identify markers of increased risk of bronchopulmonary pathology. Materials and methods. In 90 people with bronchopulmonary pathology and 124 respondents who worked in the same working conditions but had no history of diseases of the respiratory system, polymerase chain reaction in real time studied the polymorphism of DNA repair genes: XRCC7 (rs7003908), ATM (rs664677) and MLH1 (rs1799977). Results. It was found that the genotypes ATM×T/T and MLH1×A/G are associated with the risk of bronchopulmonary pathology. Genotypes that contribute to resistance to the development of respiratory system pathology were also established: ATM×A/A, ATM× A/T and MLH1×A/A. Conclusion. Genotypes associated with the risk of bronchopulmonary pathology were established: ATM×T/T (р≤0.01, χ2=6.61; OR=2.48; 95%CI: 1.16–5.31) and MLH1×A/G (p≤0.002, χ2=9.00; OR=2.32; 95%CI: 1.29–4.21). Also determined the genotypes that contribute to resistance to the development of diseases of the respiratory system: ATM×a/A (OR=0,83; 95%CI: 0,45–1,54), ATM×A/T (OR=0,67; 95% CI: 0,38–1,21) and MLH1× a/A (р≤0,003, χ2=8,73; OR=0,43; 95% CI: 0,24–0,79).

scholarly journals Diagnostic chest X-rays and breast cancer risk among women with a hereditary predisposition to breast cancer unexplained by a BRCA1 or BRCA2 mutation

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Maximiliano Ribeiro Guerra ◽  
Juliette Coignard ◽  
Séverine Eon-Marchais ◽  
Marie-Gabrielle Dondon ◽  
Dorothée Le Gal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Logistic Regression ◽  
Dna Repair Genes ◽  
X Rays ◽  
Repair Gene ◽  
X Ray ◽  
Dna Repair Gene ◽  
Chest X Ray ◽  
Repair Genes

Abstract Background Diagnostic ionizing radiation is a risk factor for breast cancer (BC). BC risk increases with increased dose to the chest and decreases with increased age at exposure, with possible effect modification related to familial or genetic predisposition. While chest X-rays increase the BC risk of BRCA1/2 mutation carriers compared to non-carriers, little is known for women with a hereditary predisposition to BC but who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation. Methods We evaluated the effect of chest X-rays from diagnostic medical procedures in a dataset composed of 1552 BC cases identified through French family cancer clinics and 1363 unrelated controls. Participants reported their history of X-ray exposures in a detailed questionnaire and were tested for 113 DNA repair genes. Logistic regression and multinomial logistic regression models were used to assess the association with BC. Results Chest X-ray exposure doubled BC risk. A 3% increased BC risk per additional exposure was observed. Being 20 years old or younger at first exposure or being exposed before first full-term pregnancy did not seem to modify this risk. Birth after 1960 or carrying a rare likely deleterious coding variant in a DNA repair gene other than BRCA1/2 modified the effect of chest X-ray exposure. Conclusion Ever/never chest X-ray exposure increases BC risk 2-fold regardless of age at first exposure and, by up to 5-fold when carrying 3 or more rare variants in a DNA repair gene. Further studies are needed to evaluate other DNA repair genes or variants to identify those which could modify radiation sensitivity. Identification of subpopulations that are more or less susceptible to ionizing radiation is important and potentially clinically relevant.

scholarly journals Polymorphism of DNA repair genes XRCC1 280, XRCC1 194, XRCC1 339 and XPD 751 with stomach cancer

2011 ◽  
Vol 10 (6) ◽  
pp. 35-39
Author(s):  
S. S. Rakitin ◽  
A. I. Dmitriyeva ◽  
V. V. Novitsky ◽  
I. A. Kuznetsova ◽  
B. A. Avkhimenko
Keyword(s):  
Gastric Cancer ◽  
Dna Repair ◽  
Excision Repair ◽  
Molecular Genetic ◽  
Dna Repair Genes ◽  
Repair Gene ◽  
Relative Risks ◽  
Polymorphic Variants ◽  
Gastric Cancer Patients ◽  
Repair Genes

We evaluated the frequency distribution of polymorphic variants in DNA repair genes XRCC1 280, XRCC1 194, XRCC1 399 and XPD 751 gastric cancer patients and healthy controls, leading to new fundamental knowledge and molecular genetic markers of gastric cancer. Statistically significant differences were identified in the two groups for the three excision repair gene XRCC1 280, XRCC1 399 and XPD 751, relative risks were calculated of gastric cancer in carriers of the minor variants of these genes.

Truncating variants in DNA-repair genes and their effect on AAO of hereditary breast cancer

2018 ◽  
Author(s):  
I Sepahi ◽  
U Faust ◽  
M Sturm ◽  
K Bosse ◽  
M Kehrer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Hereditary Breast Cancer ◽  
Dna Repair Genes ◽  
Repair Genes
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