Participants in a study of occupational exposure to mineral fibres in Slovakia were analysed for the polymorphism 23A-->G in the DNA repair gene XPA. Of the 388 subjects, 239 were exposed to asbestos, stonewool or glass fibre; the rest were unexposed controls. Levels of DNA base alterations (oxidation and alkylation) in lymphocytes were measured using the comet assay with lesion-specific endonucleases. 8-oxoguanine DNA glycosylase (OGG1) DNA repair activity was measured, as incision activity of a lymphocyte extract on DNA containing the OGG1 substrate 8-oxoguanine. Presence of the A allele was associated with higher levels of DNA damage (sites sensitive to formamidopyrimidine DNA glycosylase, endonuclease III or 3-methyladenine DNA glycosylase II) as well as with higher activity of OGG1 repair enzyme. DNA base damage increased with age, showing highly significant correlations when the whole population or subgroups of the population were analysed. OGG1 repair activity also increased with age, but when analysed according to XPA genotype, the increase was observed only in those individuals with an A allele. Although XPA is known as a protein involved in nucleotide excision repair of UV-induced damage and bulky DNA adducts, it may also have a role in the repair of oxidized bases.

Download full-text PDF

Source
http://dx.doi.org/10.1093/mutage/gel016DOI Listing

Publication Analysis

Top Keywords

dna glycosylase
12
dna
11
repair
8
dna damage
8
dna repair
8
levels dna
8
dna base
8
repair activity
8
ogg1 repair
8
increased age
8

Similar Publications

Formamidopyrimidine DNA glycosylase (Fpg) and flap endonuclease 1 (FEN1) are essential to sustaining genomic stability and integrity, while the abnormal activities of Fpg and FEN1 may lead to various diseases and cancers. The development of simple methods for simultaneously monitoring Fpg and FEN1 is highly desirable. Herein, we construct a multiple cyclic ligation-promoted exponential recombinase polymerase amplification (RPA) platform for sensitive and simultaneous monitoring of Fpg and FEN1 in cells and clinical tissues.

View Article and Find Full Text PDF

Neomorphic leukemia-derived mutations in the TET2 enzyme induce genome instability via a substrate shift from 5-methylcytosine to thymine.

Proc Natl Acad Sci U S A

February 2025

Center for Medical Research and Innovation, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, Chinese Academy of Medical Sciences (RU069), Medical College of Fudan University, Shanghai 201399, China.

Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (mC) in DNA, contributing to the regulation of gene transcription. Diverse mutations of TET2 are frequently found in various blood cancers, yet the full scope of their functional consequences has been unexplored. Here, we report that a subset of TET2 mutations identified in leukemia patients alter the substrate specificity of TET2 from acting on mC to thymine.

View Article and Find Full Text PDF

Abnormal base excision repair (BER) pathway and N6-methyladenosine (m6A) of RNA have been proved to be significantly related to age-related cataract (ARC) pathogenesis. However, the relationship between the Nei Endonuclease VIII-Like1 (NEIL1) gene (a representative DNA glycosylase of BER pathway) and its m6A modification remains unclear. Here, we showed that the expression of NEIL1 was decreased in the ARC anterior lens capsules and HO-stimulated SRA01/04 cells.

View Article and Find Full Text PDF
Article Synopsis
  • This study investigated the presence of rare germline variants in DNA damage response (DDR) genes among lung cancer patients and healthy controls, focusing on non-Hispanic Whites and African Americans.
  • Researchers analyzed data from 3,040 participants and found that lung cancer cases had a higher occurrence of these pathogenic variants compared to controls, particularly among those with adenocarcinoma.
  • The findings suggest that specific DDR gene variants are linked to lung cancer risk, especially in never smokers and those not qualifying for current screening guidelines, indicating the need for further research in these groups.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!