Laboratoire Lésions des Acides Nucléiques, Grenoble Cedex 9, France.
Published: March 2011
AI Article Synopsis
Article Abstract
Base Excision Repair (BER) is the predominant repair pathway responsible for removal of so-called small DNA lesions such as abasic sites (AP site), uracil (U), 8-oxo-7,8-dihydroguanine (8oxoG), thymine glycol (Tg). In this study, we investigated effect of aging on excision efficacy of several endogenous base lesions and AP sites using an in vitro multiplexed fluorescent approach on support (parallelized oligonucleotide cleavage assay). Human fibroblasts nuclear extracts from 29 donors of different ages were characterized in their ability to simultaneously excise the different lesions. Clearly, three different groups of lesions emerged according to the efficiency of their cleavage: one exhibited very high cleavage efficiency (AP sites and U paired with G), one showed intermediate cleavage efficiency (U paired with A and Tg). The third group included 8oxoG, A paired with 8oxoG, T at CpG site and hypoxanthine (Hx) and displayed poor repair. Aging was significantly associated with modification of excision efficiency for AP sites, uracil, Tg and 8oxoG. Repair rate decreased for the first three lesions and the most drastic effects were observed for repair of U:A. Surprisingly, excision of 8oxoG increased with aging suggesting a completely different regulation or adaptation for the initiation step of this related specific repair pathway.
Apurinic/apyrimidinic endonuclease 1 (APE1) is a central enzyme in the base excision repair (BER) pathway. APE1 catalyzes incision of the phosphodiester linkage on the 5'-side of apurinic/apyrimidinic (AP) sites during the repair of damaged nucleobases in cellular DNA. Inhibition of this enzyme can potentiate the action of DNA-damaging chemotherapeutic agents.
8-oxoguanine (8-oxoG) is a common oxidative DNA lesion that causes G > T substitutions. Determinants of local and regional differences in 8-oxoG-induced mutability across genomes are currently unknown. Here, we show DNA oxidation induces G > T substitutions and insertion/deletion (INDEL) mutations in human cells and cancers.
Objectives: To introduce a novel technique using the buried-guided suture method for suspending the alar crus to correct nostril exposure in East Asians and to investigate its safety and efficacy.
Methods: Patients with ptotic alar crus and nostril exposure at our clinic were enrolled between December 2011 and December 2023. Via an intranasal incision, the excess skin on the inner side of the nostrils was excised.
Acetaldehyde is the primary metabolite of alcohol and is present in many environmental sources including tobacco smoke. Acetaldehyde is genotoxic, whereby it can form DNA adducts and lead to mutagenesis. Individuals with defects in acetaldehyde clearance pathways have increased susceptibility to alcohol-associated cancers.
Wise Laboratory for Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, 500 S Preston Street, Building 55A, Room 1422, Louisville, KY 40292, United States. Electronic address:
Hexavalent chromium [Cr(VI)] is a human lung carcinogen with widespread exposure. How Cr(VI) causes cancer is poorly understood, but chromosome instability plays a central role. Inhibition of DNA repair pathways leads to chromosome instability; however, despite the importance of these pathways in the mechanism of Cr(VI)-induced lung carcinogenesis, there are no data considering in-depth analysis on the transcriptional changes of genes involved in them.
