Prophylaxis of oxidative DNA damage by formamidopyrimidine-DNA glycosylase

2006 ◽  
Vol 119 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Guido Frosina
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Dna Glycosylase

scholarly journals BCR-ABL1 kinase inhibits uracil DNA glycosylase UNG2 to enhance oxidative DNA damage and stimulate genomic instability

Leukemia ◽  
2012 ◽  
Vol 27 (3) ◽  
pp. 629-634 ◽  
Author(s):  
A Slupianek ◽  
R Falinski ◽  
P Znojek ◽  
T Stoklosa ◽  
S Flis ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genomic Instability ◽  
Oxidative Dna Damage ◽  
Dna Glycosylase ◽  
Uracil Dna Glycosylase

scholarly journals Evidence that OGG1 Glycosylase Protects Neurons against Oxidative DNA Damage and Cell Death under Ischemic Conditions

2010 ◽  
Vol 31 (2) ◽  
pp. 680-692 ◽  
Author(s):  
Dong Liu ◽  
Deborah L Croteau ◽  
Nadja Souza-Pinto ◽  
Michael Pitta ◽  
Jingyan Tian ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cortical Neurons ◽  
Oxidative Dna Damage ◽  
Nuclear Dna ◽  
Excision Repair ◽  
Mitochondrial Fission ◽  
Metabolic Stress ◽  
Artery Occlusion ◽  
Dna Glycosylase ◽  
Base Excision

7,8-Dihydro-8-oxoguanine DNA glycosylase (OGG1) is a major DNA glycosylase involved in base-excision repair (BER) of oxidative DNA damage to nuclear and mitochondrial DNA (mtDNA). We used OGG1-deficient (OGG1−/–) mice to examine the possible roles of OGG1 in the vulnerability of neurons to ischemic and oxidative stress. After exposure of cultured neurons to oxidative and metabolic stress levels of OGG1 in the nucleus were elevated and mitochondria exhibited fragmentation and increased levels of the mitochondrial fission protein dynamin-related protein 1 (Drp1) and reduced membrane potential. Cortical neurons isolated from OGG1−/– mice were more vulnerable to oxidative insults than were OGG1+/+ neurons, and OGG1−/– mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1+/+ mice. Accumulations of oxidative DNA base lesions (8-oxoG, FapyAde, and FapyGua) were elevated in response to ischemia in both the ipsilateral and contralateral hemispheres, and to a greater extent in the contralateral cortex of OGG1−/– mice compared with OGG1+/+ mice. Ischemia-induced elevation of 8-oxoG incision activity involved increased levels of a nuclear isoform OGG1, suggesting an adaptive response to oxidative nuclear DNA damage. Thus, OGG1 has a pivotal role in repairing oxidative damage to nuclear DNA under ischemic conditions, thereby reducing brain damage and improving functional outcome.

scholarly journals Role of a MutY DNA glycosylase in combating oxidative DNA damage in Helicobacter pylori

DNA Repair ◽  
2007 ◽  
Vol 6 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Rory Eutsey ◽  
Ge Wang ◽  
Robert J. Maier
Keyword(s):  
Dna Damage ◽  
Helicobacter Pylori ◽  
Oxidative Dna Damage ◽  
Dna Glycosylase

scholarly journals Genetic variation in the NEIL2 DNA glycosylase gene is associated with oxidative DNA damage in BRCA2 mutation carriers

Oncotarget ◽  
2017 ◽  
Vol 8 (70) ◽  
pp. 114626-114636 ◽  
Author(s):  
Carlos Benítez-Buelga ◽  
Juan Miguel Baquero ◽  
Tereza Vaclova ◽  
Victoria Fernández ◽  
Paloma Martín ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genetic Variation ◽  
Oxidative Dna Damage ◽  
Brca2 Mutation ◽  
Dna Glycosylase ◽  
Mutation Carriers

A novel patient-derived cell line of adrenocortical carcinoma shows a pathogenic role of germline MUTYH mutation and high tumour mutational burden

2021 ◽  
Author(s):  
Laura-Sophie Landwehr ◽  
Jochen Schreiner ◽  
Silke Appenzeller ◽  
Stefan Kircher ◽  
Sabine Herterich ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Line ◽  
Adrenocortical Carcinoma ◽  
Oxidative Dna Damage ◽  
Cell Model ◽  
Primary Tumour ◽  
Tumour Suppressor Gene ◽  
Dna Glycosylase ◽  
Single Nucleotide Variants ◽  
Mutational Burden

Background The response of advanced adrenocortical carcinoma (ACC) to current chemotherapies is unsatisfactory and a limited rate of response to immunotherapy was observed in clinical trials. High tumour mutational burden (TMB) and the presence of a specific DNA signature are characteristic features of tumours with mutations in the gene MUTYH encoding the mutY DNA glycosylase. Both have been shown to potentially predict the response to immunotherapy. High TMB in an ACC cell line model has not been reported yet. Design and Methods The JIL-2266 cell line was established from a primary ACC tumour, comprehensively characterised and oxidative damage, caused by a dysfunctional mutY DNA glycosylase, confirmed. Results Here, we characterise the novel patient-derived ACC cell line JIL-2266, which is deficient in MUTYH-dependent DNA repair. JIL-2266 cells have a consistent STR marker profile that confirmed congruousness with primary ACC tumour. Cells proliferate with a doubling time of 41±13 hours. Immunohistochemistry revealed positivity for steroidogenic factor-1. Mass spectrometry did not demonstrate significant steroid hormone synthesis. JIL-2266 have hemizygous mutations in the tumour suppressor gene TP53 (c.859G>T:p.E287X) and MUTYH (c.316C>T:p.R106W). Exome sequencing showed 683 single nucleotide variants and 4 insertions/deletions. We found increased oxidative DNA damage in the cell line and the corresponding primary tumour caused by impaired mutY DNA glycosylase function and accumulation of 8-oxoguanine. Conclusion This model will be valuable as a pre-clinical ACC cell model with high TMB and a tool to study oxidative DNA damage in the adrenal gland.

scholarly journals Helicobacter pylori infection downregulates the DNA glycosylase NEIL2, resulting in increased genome damage and inflammation in gastric epithelial cells

2020 ◽  
Vol 295 (32) ◽  
pp. 11082-11098 ◽  
Author(s):  
Ibrahim M. Sayed ◽  
Ayse Z. Sahan ◽  
Tatiana Venkova ◽  
Anirban Chakraborty ◽  
Dibyabrata Mukhopadhyay ◽  
...  
Keyword(s):  
Dna Damage ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Oxidative Dna Damage ◽  
Expression Profiles ◽  
Dna Glycosylase ◽  
Gastric Epithelial Cells ◽  
Genome Damage ◽  
H Pylori

Infection with the Gram-negative, microaerophilic bacterium Helicobacter pylori induces an inflammatory response and oxidative DNA damage in gastric epithelial cells that can lead to gastric cancer (GC). However, the underlying pathogenic mechanism is largely unclear. Here, we report that the suppression of Nei-like DNA glycosylase 2 (NEIL2), a mammalian DNA glycosylase that specifically removes oxidized bases, is one mechanism through which H. pylori infection may fuel the accumulation of DNA damage leading to GC. Using cultured cell lines, gastric biopsy specimens, primary cells, and human enteroid-derived monolayers from healthy human stomach, we show that H. pylori infection greatly reduces NEIL2 expression. The H. pylori infection-induced downregulation of NEIL2 was specific, as Campylobacter jejuni had no such effect. Using gastric organoids isolated from the murine stomach in coculture experiments with live bacteria mimicking the infected stomach lining, we found that H. pylori infection is associated with the production of various inflammatory cytokines. This response was more pronounced in Neil2 knockout (KO) mouse cells than in WT cells, suggesting that NEIL2 suppresses inflammation under physiological conditions. Notably, the H. pylori-infected Neil2-KO murine stomach exhibited more DNA damage than the WT. Furthermore, H. pylori-infected Neil2-KO mice had greater inflammation and more epithelial cell damage. Computational analysis of gene expression profiles of DNA glycosylases in gastric specimens linked the reduced Neil2 level to GC progression. Our results suggest that NEIL2 downregulation is a plausible mechanism by which H. pylori infection impairs DNA damage repair, amplifies the inflammatory response, and initiates GC.

Sign in / Sign up

Export Citation Format

Share Document