i
Defects in Base Excision Repair Sensitize Cells to Manganese in S. cerevisiae
-
Oct 27 2013
Source: Biomed Res Int. 2013; 2013. -
Alternative Title:Biomed Res Int
-
Publisher's site:
-
Personal Author:
-
Description:Manganese (Mn) is essential for normal physiologic functioning; therefore, deficiencies and excess intake of manganese can result in disease. In humans, prolonged exposure to manganese causes neurotoxicity characterized by Parkinson-like symptoms. Mn(2+) has been shown to mediate DNA damage possibly through the generation of reactive oxygen species. In a recent publication, we showed that Mn induced oxidative DNA damage and caused lesions in thymines. This study further investigates the mechanisms by which cells process Mn(2+)-mediated DNA damage using the yeast S. cerevisiae. The strains most sensitive to Mn(2+) were those defective in base excision repair, glutathione synthesis, and superoxide dismutase mutants. Mn(2+) caused a dose-dependent increase in the accumulation of mutations using the CAN1 and lys2-10A mutator assays. The spectrum of CAN1 mutants indicates that exposure to Mn results in accumulation of base substitutions and frameshift mutations. The sensitivity of cells to Mn(2+) as well as its mutagenic effect was reduced by N-acetylcysteine, glutathione, and Mg(2+). These data suggest that Mn(2+) causes oxidative DNA damage that requires base excision repair for processing and that Mn interferes with polymerase fidelity. The status of base excision repair may provide a biomarker for the sensitivity of individuals to manganese.
-
Subject:
-
Source:
-
Pubmed ID:24282812
-
Pubmed Central ID:PMC3825218
-
Document Type:
-
Funding:
-
Collection(s):
-
Main Document Checksum:
-
Download URL:
-
File Type:
-
gif jpeg txt txt gif jpeg gif jpeg gif jpeg gif jpeg
Details:
Supporting Files
More +