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Accelerated repair and reduced mutagenicity of oxidative DNA damage in human bladder cells expressing the E. coli FPG protein
Author(s) -
Ropolo Monica,
Geroldi Alessandro,
Degan Paolo,
Andreotti Virginia,
Zupo Simona,
Poggi Alessandro,
Reed April,
Kelley Mark R.,
Frosina Guido
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21554
Subject(s) - dna glycosylase , dna repair , base excision repair , dna damage , uracil dna glycosylase , nucleotide excision repair , ap site , microbiology and biotechnology , chemistry , dna , oxidative phosphorylation , biochemistry , biology
Repair of some oxidized purines such as 8‐oxo‐7,8‐dihydroguanine (8‐oxoG) is inefficient in human cells in comparison to repair of other major endogenous lesions ( e.g. uracil, abasic sites or oxidized pyrimidines). This is due to the poor catalytic properties of hOGG1, the major DNA glycosylase involved in 8‐oxoG removal. The formamidopyrimidine DNA glycosylase (FPG) protein from E. coli is endowed with a potent 8‐oxoG glycolytic activity coupled with a β,δ‐AP lyase. In this study, we have expressed FPG fused to the enhanced green fluorescent protein (EGFP) in human bladder cells to accelerate the repair of oxidative DNA damage. Cells expressing the fusion protein EGFP–FPG repaired 8‐oxoG and AP sites at accelerated rates, in particular via the single‐nucleotide insertion base excision repair (BER) pathway and were resistant to mutagenicity of the oxidizing carcinogen potassium bromate. FPG may stably protect human cells from some harmful effects of oxidative DNA damage. © 2005 Wiley‐Liss, Inc.