Search results for "Glycosylase"
showing 3 items of 53 documents
BER, MGMT, and MMR in defense against alkylation-induced genotoxicity and apoptosis
2001
Methylating carcinogens and cytostatic drugs induce different methylation products in DNA. In cells not expressing the repair protein MGMT or expressing it at a low level, O6-methylguanine is the major genotoxic, recombinogenic, and apoptotic lesion. Genotoxicity and apoptosis triggered by O6-methylguanine require mismatch repair (MMR). In cells expressing O6-methylguanine-DNA methyl transferase (MGMT) at a high level or for agents producing low amounts of O6-methylguanine, N-alkylations become the major genotoxic lesions. N-Alkylations are repaired by base excision repair (BER). In mammalian cells, naturally occurring mutants of BER have not been detected, which points to the importance of…
Characterization of hOGG1 Promoter Structure, Expression During Cell Cycle and Overexpression in Mammalian Cells
2001
Oxygen radicals are produced in all cells either by the normal cellular metabolism or by the exposure to external mutagens. The reactive oxygen species (ROS) generated can induce DNA damage. Among the principal lesions found in DNA due to ROS is an oxidized form of guanine, 8-oxo-7,8-dihydroguanine (8-oxoG). The biological relevance of this lesion has been unveiled by the study of Escherichia colt and Saccharomyces cerevisiae genes involved in the neutralization of the mutagenic effects of 8-oxoG (Cabrera et al., 1988; Nghiem et al., 1988; Radicella et al., 1988; van der Kemp et al., 1996). These genes fpg and mutY for E. colt and OGG1 for yeast, code for DNA glycosylases. Inactivation of a…
A global DNA repair mechanism involving the Cockayne syndrome B (CSB) gene product can prevent the in vivo accumulation of endogenous oxidative DNA b…
2002
The Cockayne syndrome B (CSB) gene product is involved in the repair of various types of base modifications in actively transcribed DNA sequences. To investigate its significance for the repair of endogenous oxidative DNA damage, homozygous csb(-/-)/ogg1(-/-) double knockout mice were generated. These combine the deficiency of CSB with that of OGG1, a gene coding for the mammalian repair glycosylase that initiates the base excision repair of 7,8-dihydro-8-oxoguanine (8-oxoG). Compared to ogg1(-/-) mice, csb(-/-)/ogg1(-/-) mice were found to accumulate with age severalfold higher levels of oxidited purine modifications in hepatocytes, splenocytes and kidney cells. In contrast, the basal (ste…