Decline of nuclear and mitochondrial oxidative base excision repair activity in late passage human diploid fibroblasts

Shen, Guang-Ping; Galick, Heather; Inoue, Masaaki; Wallace, Susan S.

doi:10.1016/s1568-7864(03)00006-5

Cited by 36 publications

(13 citation statements)

References 80 publications

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“…Furthermore, a significant decrease in the mitochondrial incision activity of 8-oxoG-DNA glycosylase, uracil-DNA glycosylase, and the endonuclease III homolog was found in the brains of old mice, whereas smaller changes were observed in nuclear incision activity [97][98][99]. Similarly, a decline in cleavage activity was observed in mitochondrial and, to a lesser extent, in nuclear extracts from senescent human fibroblasts [100]. A different in vitro assay measuring the repair of the synthetic DNA substrate containing a single G:U mismatch showed a strong decline in BER activity in brain, liver, and germ-cell nuclear extracts of old mice [101].…”

Section: Dna Oxidation and Repairmentioning

confidence: 89%

Nucleic acid oxidation in Alzheimer disease

Moreira

Nunomura

Nakamura

et al. 2008

Free Radical Biology and Medicine

187

113

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Increasing evidence suggests that oxidative stress is intimately associated with Alzheimer disease pathophysiology. Nucleic acids (nuclear DNA, mitochondrial DNA, and RNA) are one of the several cellular macromolecules damaged by reactive oxygen species, particularly the hydroxyl radical. Because neurons are irreplaceable and survive as long as the organism does, they need elaborate defense mechanisms to ensure their longevity. In Alzheimer disease, however, an accumulation of nucleic acid oxidation is observed, indicating an increased level of oxidative stress and/or a decreased capacity to repair the nucleic acid damage. In this review, we present data supporting the notion that mitochondrial and metal abnormalities are key sources of oxidative stress in Alzheimer disease. Furthermore, we outline the mechanisms of nucleic acid oxidation and repair. Finally, evidence showing the occurrence of nucleic acid oxidation in Alzheimer disease will be discussed.

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Section: Dna Oxidation and Repairmentioning

confidence: 89%

Nucleic acid oxidation in Alzheimer disease

Moreira

Nunomura

Nakamura

et al. 2008

Free Radical Biology and Medicine

187

113

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“…The efficiency and fidelity of some DNA repair pathways such as base excision repair and NHEJ have been shown to decrease with age [4][5][6][7]66,67]. Here, we measured recombination using two independent methods: we assessed the rate of recombination at the FYDR locus (which is designed to measure not only exchanges between sister chromatids, but also gene conversions in the absence of crossovers), and we also measured the frequency of SCEs.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations are believed to accumulate with age due to a combination of increased levels of endogenous DNA damaging agents, such as reactive oxygen species [3], and decreased efficiency and fidelity of DNA repair [4][5][6][7][8]. Double strand breaks (DSBs) are considered to be among the most toxic and mutagenic lesions that mammalian cells experience.…”

Section: Introductionmentioning

confidence: 99%

Tissue-specific differences in the accumulation of sequence rearrangements with age

et al. 2008

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Mitotic homologous recombination (HR) is a critical pathway for the accurate repair of DNA double strand breaks (DSBs) and broken replication forks. While generally error-free, HR can occur between misaligned sequences, resulting in deleterious sequence rearrangements that can contribute to cancer and aging. To learn more about the extent to which HR occurs in different tissues during the aging process, we used Fluorescent Yellow Direct Repeat (FYDR) mice in which an HR event in a transgene yields a fluorescent phenotype. Here, we show tissue-specific differences in the accumulation of recombinant cells with age. Unlike pancreas, which shows a dramatic 23-fold increase in recombinant cell frequency with age, skin shows no increase in vivo. In vitro studies indicate that juvenile and aged primary fibroblasts are similarly able to undergo HR in response to endogenous and exogenous DNA damage. Therefore, the lack of recombinant cell accumulation in the skin is most likely not due to an inability to undergo de novo HR events. We propose that tissue-specific differences in the accumulation of recombinant cells with age result from differences in the ability of recombinant cells to persist and clonally expand within tissues.

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“…Several reports have associated mtDNA mutations and deletions with Alzheimer’s disease (AD) (Chang et al, 2000; Hutchin et al, 1995; Davis et al, 1997; Coskun et al, 2004; Lin and Beal, 2006) and recent data show that a significant decline in total BER takes place in the cortical area of AD patients (Weissman et al, 2007). Moreover, it has been reported that targeting hOGG1 into mitochondria increases survival and protects against induced-oxidative stress in various cell types including oligodendrocytes and INS-1 cells (Druzhyna et al, 2003; Rachek et al, 2006), and that mitochondrial BER activity decreases in cultured human fibroblast with higher passage number (Shen et al, 2003). …”

Section: Base Excision Repair: a Conserved Mechanism Involved In Tmentioning

confidence: 99%

Mitochondrial DNA repair and association with aging – An update

Gredilla

Bohr

Stevnsner

2010

Experimental Gerontology

134

124

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Mitochondrial DNA is constantly exposed to oxidative injury. Due to its location close to the main site of reactive oxygen species, the inner mitochondrial membrane, mtDNA is more susceptible than nuclear DNA to oxidative damage. The accumulation of DNA damage is thought to play a critical role in the aging process and to be particularly deleterious in post-mitotic cells. Thus, DNA repair is an important mechanism for maintenance of genomic integrity. Despite the importance of mitochondria in the aging process, it was thought for many years that mitochondria lacked an enzymatic DNA repair system comparable to that in the nuclear compartment. However, it is now well established that DNA repair actively takes place in mitochondria. Oxidative DNA damage processing, base excision repair mechanisms were the first to be described in these organelles, and consequently the best understood. However, new proteins and novel DNA repair pathways, thought to be exclusively present in the nucleus, have recently been described also to be present in mitochondria. Here we review the main mitochondrial DNA repair pathways and their association with the aging process.

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Decline of nuclear and mitochondrial oxidative base excision repair activity in late passage human diploid fibroblasts

Cited by 36 publications

References 80 publications

Nucleic acid oxidation in Alzheimer disease

Nucleic acid oxidation in Alzheimer disease

Tissue-specific differences in the accumulation of sequence rearrangements with age

Mitochondrial DNA repair and association with aging – An update

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