Gene-specific nuclear and mitochondrial repair of formamidopyrimidine DNA glycosylase-sensitive sites in Chinese hamster ovary cells

Taffe, Bonita G.; Larminat, Florence; Laval, Jacques; Croteau, Deborah L.; Anson, R. Michael; Bohr, Vilhelm A.

doi:10.1016/s0921-8777(96)00031-6

Cited by 68 publications

(34 citation statements)

References 42 publications

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“…One of the most common oxidative DNA lesions is 7,8-dihydroxyguanine (8-oxoG). Mitochondria efficiently repair 8-oxoG and other damage to DNA bases (Anson et al, 1998;LeDoux et al, 1992;Taffe et al, 1996), but have no capacity to repair UV-induced pyrimidine dimers (Clayton et al, 1974).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial repair of 8-oxoguanine is deficient in Cockayne syndrome group B

et al. 2002

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Section: Introductionmentioning

confidence: 99%

Mitochondrial repair of 8-oxoguanine is deficient in Cockayne syndrome group B

et al. 2002

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“…Cells that were treated with a damaging agent and allowed to repair the induced damage, also repaired the endogenous damage (142,144). Studies in our own laboratory failed to confirm this, due to the absence of endogenous damage observed in the mtDNA of control cells (147,146). The reason for the discrepancy is not known.…”

Section: Removal Of Damage From Mtdna (And Removal Of Damaged Mtdna)mentioning

confidence: 81%

Mitochondria, oxidative DNA damage, and aging

Anson

Bohr

2000

AGE

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Protection from reactive oxygen species (ROS) and from mitochondrial oxidative damage is well known to be necessary to longevity. The relevance of mitochondrial DNA (mtDNA) to aging is suggested by the fact that the two most commonly measured forms of mtDNA damage, deletions and the oxidatively induced lesion 8-oxo-dG, increase with age. The rate of increase is species-specific and correlates with maximum lifespan.It is less clear that failure or inadequacies in the protection from reactive oxygen species (ROS) and from mitochondrial oxidative damage are sufficient to explain senescence. DNA containing 8-oxo-dG is repaired by mitochondria, and the high ratio of mitochondrial to nuclear levels of 8-oxo-dG previously reported are now suspected to be due to methodological difficulties. Furthermore, MnSOD -/+ mice incur higher than wild type levels of oxidative damage, but do not display an aging phenotype. Together, these findings suggest that oxidative damage to mitochondria is lower than previously thought, and that higher levels can be tolerated without physiological consequence.A great deal of work remains before it will be known whether mitochondrial oxidative damage is a "clock" which controls the rate of aging. The increased level of 8-oxo-dG seen with age in isolated mitochondria needs explanation. It could be that a subset of cells lose the ability to protect or repair mitochondria, resulting in their incurring disproportionate levels of damage. Such an uneven distribution could exceed the reserve capacity of these cells and have serious physiological consequences.

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“…Previous studies from this laboratory and others suggested that mitochondria may contain a glycosylase/lyase enzyme responsible for the removal of oxidative damage (13,17). In our recent study on the repair of oxidative damage in mitochondria, Chinese hamster ovary cells were exposed to acridine orange plus light for the purpose of introducing 8-oxoG and other oxidative DNA damage lesions (13).…”

mentioning

confidence: 99%

“…In our recent study on the repair of oxidative damage in mitochondria, Chinese hamster ovary cells were exposed to acridine orange plus light for the purpose of introducing 8-oxoG and other oxidative DNA damage lesions (13). The DNA repair profile showed that these lesions were rapidly removed from the mitochondrial genome with more than 60% of the lesions repaired within 4 h, suggesting that mammalian cells possess mitochondrial enzymes that recognize and remove 8-oxoG.…”

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confidence: 99%

An Oxidative Damage-specific Endonuclease from Rat Liver Mitochondria

Croteau

Rhys

Hudson

et al. 1997

Journal of Biological Chemistry

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147

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Reactive oxygen species have been shown to generate mutagenic lesions in DNA. One of the most abundant lesions in both nuclear and mitochondrial DNA is 7,8-dihydro-8-oxoguanine (8-oxoG). We report here the partial purification and characterization of a mitochondrial oxidative damage endonuclease (mtODE) from rat liver that recognizes and incises at 8-oxoG and abasic sites in duplex DNA. Rat liver mitochondria were purified by differential and Percoll gradient centrifugation, and mtODE was extracted from Triton X-100-solubilized mitochondria. Incision activity was measured using a radiolabeled double-stranded DNA oligonucleotide containing a unique 8-oxoG, and reaction products were separated by polyacrylamide gel electrophoresis. Gel filtration chromatography predicts mtODE's molecular mass to be between 25 and 30 kDa. mtODE has a monovalent cation optimum between 50 and 100 mM KCl and a pH optimum between 7.5 and 8. mtODE does not require any co-factors and is active in the presence of 5 mM EDTA. It is specific for 8-oxoG and preferentially incises at 8-oxoG:C base pairs. mtODE is a putative 8-oxoG glycosylase/lyase enzyme, because it can be covalently linked to the 8-oxoG oligonucleotide by sodium borohydride reduction. Comparison of mtODE's activity with other known 8-oxoG glycosylases/lyases and mitochondrial enzymes reveals that this may be a novel protein.Reactive oxygen species are generated in cells as a by-product of cellular respiration. Reactive oxygen species react with proteins, lipids and DNA causing cellular damage. When DNA is the target, a variety of DNA adducts are formed. Among these, 8-oxoG is one of the most abundant lesions generated (1, 2). 8-oxoG 1 is considered to be a premutagenic lesion because it can mispair with adenine during DNA replication (3-5). In the absence of DNA repair, this mispairing results in G to T transversion mutations. Since many reactive oxygen species are generated by oxidative processes that occur in mitochondria, it is of great interest to understand the oxidative DNA damage processing in these organelles.Mitochondrial DNA (mtDNA) is composed of a 16.5-kilobase pair circular genome, encoding 13 structural genes, 22 tRNAs, and two rRNAs. The DNA lies in close proximity to the free radical-producing electron transport chain, and it has been reported that mtDNA contains a higher level of oxidative DNA damage than nuclear DNA (6). Since mtDNA is subjected to relatively high levels of oxidative damage, mitochondria need DNA repair mechanisms to maintain their DNA genomes.Mitochondrial DNA repair mechanisms differ from those in the nucleus. Evidence to suggest that mitochondria lacked DNA repair mechanisms came from the observation that UV damage is not repaired in mitochondria (7, 8), while it is efficiently processed in the nucleus by nucleotide excision repair. In addition, damage caused by cisplatin and nitrogen mustard, agents that are known to induce DNA adducts that are substrates for the nuclear nucleotide excision repair pathway, is inefficiently repaired in m...

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Gene-specific nuclear and mitochondrial repair of formamidopyrimidine DNA glycosylase-sensitive sites in Chinese hamster ovary cells

Cited by 68 publications

References 42 publications

Mitochondrial repair of 8-oxoguanine is deficient in Cockayne syndrome group B

Mitochondrial repair of 8-oxoguanine is deficient in Cockayne syndrome group B

Mitochondria, oxidative DNA damage, and aging

An Oxidative Damage-specific Endonuclease from Rat Liver Mitochondria

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