Oxidative DNA damage, antioxidants and DNA repair: applications of the comet assay

2001 ◽  
Vol 29 (2) ◽  
pp. 337-340 ◽  
Author(s):  
A. R. Collins ◽  
E. Horváthová
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Oxidative Dna Damage ◽  
White Blood Cells ◽  
State Level ◽  
Dna Oxidation ◽  
Concerted Action ◽  
European Standards ◽  
Human White Blood Cells ◽  
Oxidative Base Damage

Estimates of background levels of oxidative base damage in human white blood cells vary enormously, from 300 down to 0.4 molecules of 8-oxoguanine per 106 guanines. An EC-funded Concerted Action, the European Standards Committee on Oxidative DNA Damage, is currently attempting to resolve the discrepancy and to agree a realistic estimate of basal endogenous oxidation. Oxidation of lymphocyte DNA is a useful marker of oxidative stress, and this can be decreased by supplementation with pure antioxidants or with foods rich in antioxidants. The steady-state level of DNA oxidation is ultimately controlled by the process of DNA repair; the extent to which this varies between individuals has yet to be established.

scholarly journals The transcription-coupled DNA repair-initiating protein CSB promotes XRCC1 recruitment to oxidative DNA damage

2018 ◽  
Vol 46 (15) ◽  
pp. 7747-7756 ◽  
Author(s):  
Hervé Menoni ◽  
Franziska Wienholz ◽  
Arjan F Theil ◽  
Roel C Janssens ◽  
Hannes Lans ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Oxidative Dna Damage

Mutations in CREBBP and EP300 genes affect DNA repair of oxidative damage in Rubinstein-Taybi syndrome cells

2019 ◽  
Vol 41 (3) ◽  
pp. 257-266
Author(s):  
Ilaria Dutto ◽  
Claudia Scalera ◽  
Micol Tillhon ◽  
Giulio Ticli ◽  
Gianluca Passaniti ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Genome Stability ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Control Cell ◽  
Nuclear Antigen ◽  
Autosomal Dominant Disorder ◽  
Cell Extracts ◽  
Increased Risk

Abstract Rubinstein-Taybi syndrome (RSTS) is an autosomal-dominant disorder characterized by intellectual disability, skeletal abnormalities, growth deficiency and an increased risk of tumors. RSTS is predominantly caused by mutations in CREBBP or EP300 genes encoding for CBP and p300 proteins, two lysine acetyl-transferases (KAT) playing a key role in transcription, cell proliferation and DNA repair. However, the efficiency of these processes in RSTS cells is still largely unknown. Here, we have investigated whether pathways involved in the maintenance of genome stability are affected in lymphoblastoid cell lines (LCLs) obtained from RSTS patients with mutations in CREBBP or in EP300 genes. We report that RSTS LCLs with mutations affecting CBP or p300 protein levels or KAT activity, are more sensitive to oxidative DNA damage and exhibit defective base excision repair (BER). We have found reduced OGG1 DNA glycosylase activity in RSTS compared to control cell extracts, and concomitant lower OGG1 acetylation levels, thereby impairing the initiation of the BER process. In addition, we report reduced acetylation of other BER factors, such as DNA polymerase β and Proliferating Cell Nuclear Antigen (PCNA), together with acetylation of histone H3. We also show that complementation of CBP or p300 partially reversed RSTS cell sensitivity to DNA damage. These results disclose a mechanism of defective DNA repair as a source of genome instability in RSTS cells.

scholarly journals Dynamic Compartmentalization of Base Excision Repair Proteins in Response to Nuclear and Mitochondrial Oxidative Stress

2008 ◽  
Vol 29 (3) ◽  
pp. 794-807 ◽  
Author(s):  
Lyra M. Griffiths ◽  
Dan Swartzlander ◽  
Kellen L. Meadows ◽  
Keith D. Wilkinson ◽  
Anita H. Corbett ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Base Excision Repair ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Intracellular Localization ◽  
Genotoxic Stress ◽  
Mitochondrial Oxidative Stress ◽  
Base Excision

ABSTRACT DNAs harbored in both nuclei and mitochondria of eukaryotic cells are subject to continuous oxidative damage resulting from normal metabolic activities or environmental insults. Oxidative DNA damage is primarily reversed by the base excision repair (BER) pathway, initiated by N-glycosylase apurinic/apyrimidinic (AP) lyase proteins. To execute an appropriate repair response, BER components must be distributed to accommodate levels of genotoxic stress that may vary considerably between nuclei and mitochondria, depending on the growth state and stress environment of the cell. Numerous examples exist where cells respond to signals, resulting in relocalization of proteins involved in key biological transactions. To address whether such dynamic localization contributes to efficient organelle-specific DNA repair, we determined the intracellular localization of the Saccharomyces cerevisiae N-glycosylase/AP lyases, Ntg1 and Ntg2, in response to nuclear and mitochondrial oxidative stress. Fluorescence microscopy revealed that Ntg1 is differentially localized to nuclei and mitochondria, likely in response to the oxidative DNA damage status of the organelle. Sumoylation is associated with targeting of Ntg1 to nuclei containing oxidative DNA damage. These studies demonstrate that trafficking of DNA repair proteins to organelles containing high levels of oxidative DNA damage may be a central point for regulating BER in response to oxidative stress.

scholarly journals ROS-Induced DNA Damage Associates with Abundance of Mitochondrial DNA in White Blood Cells of the Untreated Schizophrenic Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
I. V. Chestkov ◽  
E. M. Jestkova ◽  
E. S. Ershova ◽  
V. G. Golimbet ◽  
T. V. Lezheiko ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Paranoid Schizophrenia ◽  
Venous Blood ◽  
White Blood Cells ◽  
Mtdna Copy Number ◽  
Antipsychotic Medications ◽  
Significant Difference ◽  
Schizophrenic Patients ◽  
Male Patients

Objective. The aim of this study was (1) to examine the leukocyte mtDNA copy number (CN) in unmedicated (SZ (m−)) and medicated (SZ (m+)) male patients with paranoid schizophrenia (SZ) in comparison with the healthy male controls (HC) and (2) to compare the leukocyte mtDNA CN with the content of an oxidation marker 8-oxodG in lymphocytes of the SZ (m−) patients. Methods. We evaluated leukocyte mtDNA CN of 110 subjects with SZ in comparison with 60 male HC by the method qPCR (ratio mtDNA/nDNA (gene B2M) was detected). SZ patients were divided into two subgroups. The patients of the subgroups SZ (m+) (N=55) were treated with standard antipsychotic medications in the hospital. The patients of the subgroup SZ (m−) (N=55) were not treated before venous blood was sampled. To evaluate oxidative DNA damage, we quantified the levels of 8-oxodG in lymphocytes (flow cytometry) of SZ (m−) patients (N=55) and HC (N=30). Results. The leukocyte mtDNA CN showed no significant difference in SZ (m+) patients and HC. The mtDNA CN in the unmedicated subgroup SZ (m−) was significantly higher than that in the SZ (m+) subgroup or in HC group. The level of 8-oxodG in the subgroup SZ (m−) was significantly higher than that in HC group. Conclusion. The leukocytes of the unmedicated SZ male patients with acute psychosis contain more mtDNA than the leukocytes of the male SZ patients treated with antipsychotic medications or the healthy controls. MtDNA content positively correlates with the level of 8-oxodG in the unmedicated SZ patients.

Recent Aspects of Oxidative DNA Damage: Guanine Lesions, Measurement and Substrate Specificity of DNA Repair Glycosylases

2002 ◽  
Vol 383 (6) ◽  
Author(s):  
Jean Cadet ◽  
Sophie Bellon ◽  
Maurice Berger ◽  
Anne-Gaëlle Bourdat ◽  
Thierry Douki ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Substrate Specificity ◽  
Oxidative Dna Damage

DNA repair BER pathway inhibition increases cell death caused by oxidative DNA damage in Trypanosoma cruzi

2011 ◽  
Vol 112 (8) ◽  
pp. 2189-2199 ◽  
Author(s):  
G. Cabrera ◽  
C. Barría ◽  
C. Fernández ◽  
S. Sepúlveda ◽  
L. Valenzuela ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Dna Repair ◽  
Trypanosoma Cruzi ◽  
Oxidative Dna Damage ◽  
Pathway Inhibition

Nitric oxide–mediated inhibition of DNA repair potentiates oxidative DNA damage in cholangiocytes

2001 ◽  
Vol 120 (1) ◽  
pp. 190-199 ◽  
Author(s):  
Meeta Jaiswal ◽  
Nicholas F. LaRusso ◽  
Richard A. Shapiro ◽  
Timothy R. Billiar ◽  
Gregory J. Gores
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Dna Repair ◽  
Oxidative Dna Damage
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