PURPOSE Several studies have described molecular differences between microsatellite stable hereditary nonpolyposis colorectal cancer (MSS-HNPCC) and microsatellite unstable Lynch syndrome tumors (MSI-HNPCC). These differences highlight the possibility that other instability forms could explain cancer susceptibility in this group of families. The base excision repair (BER) pathway is the major D...

8-Hydroxyguanine (8OHG), an oxidatively damaged base, and benzo[a]pyrene-diol-epoxide (BPDE), a metabolite of benzo[a]pyrene found in cigarette smoke, are thought to be major causes for G:C to T:A transversions in DNA of human cells. In this study, we assessed the abilities of OGG1, MYH and APE1 proteins, which are components of a base excision repair pathway, to suppress G:C to T:A transversio...

Oxidative DNA damage is one of the most common threats to genome stability and DNA repair enzymes provide protection from the effects of oxidized DNA bases. In mammalian cells, base excision repair (BER) mediated by the OGG1 and MYH DNA glycosylases prevents the accumulation of 8-oxoguanine (8-oxoG) in DNA. When steady-state levels of DNA 8-oxoG were measured in myh(-/-) and myh(-/-)/ogg1(-/-) ...

Oxidative stress and mitochondrial dysfunction are implicated in aging-related neurodegenerative disorders. 8-Oxoguanine (8-oxoG), a common oxidised base lesion, is often highly accumulated in brains from patients with neurodegenerative disorders. MTH1 hydrolyses 8-oxo-2'-deoxyguanosine triphosphate (8-oxo-dGTP) to 8-oxo-dGMP and pyrophosphate in nucleotide pools, while OGG1 excises 8-oxoG pair...

The airway mucosa is responsible for mounting a robust innate immune response (IIR) upon encountering pathogen-associated molecular patterns. The IIR produces protective gene networks that stimulate neighboring epithelia and components of the immune system to trigger adaptive immunity. Little is currently known about how cellular reactive oxygen species (ROS) signaling is produced and cooperate...

Hemorrhagic cystitis is an inflammatory and ulcerative bladder condition associated with systemic chemotherapeutics, like cyclophosphomide. Earlier, we reported reactive oxygen species resulting from cyclophosphamide metabolite, acrolein, causes global methylation followed by silencing of DNA damage repair genes. Ogg1 (8-oxoguanine DNA glycosylase) is one such silenced base excision repair enzy...

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 endonu...

Base excision repair (BER) may become less effective with ageing resulting in accumulation of DNA lesions, genome instability and altered gene expression that contribute to age-related degenerative diseases. The brain is particularly vulnerable to the accumulation of DNA lesions; hence, proper functioning of DNA repair mechanisms is important for neuronal survival. Although the mechanism of age...

Biallelic inherited mutations in the oxidative DNA damage repair gene MUTYH predispose to colorectal adenomas and colorectal carcinoma (CRC) with high penetrance. We investigated whether rare inherited variants in other oxidative DNA damage repair genes predisposed to CRC. Single marker association analyses were assessed under an allelic model with Bonferroni correction for multiple testing. Al...

Altered DNA repair capacity can result in increased susceptibility to cancer. The base excision repair (BER) pathway effectively removes DNA damage caused by ionizing radiation and reactive oxidative species (ROS). In the current study, we analyzed the possible relation of polymorphisms in BER genes, including 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and...