Proteins associated with mitochondrial DNA protect it against X-rays and hydrogen peroxide

Gouliaeva, N. A.; Kuznetsova, Elena; Gaziev, A.I.

doi:10.1134/s0006350906040166

Cited by 20 publications

(20 citation statements)

References 17 publications

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“…However, there is a debate about the protective role of histones, as there is also evidence showing that the electrons can transfer easily from histones to DNA leading to damage [83] and under some conditions (exposure to Cu(II)/H 2 O 2 ) histones can even enhance DNA damage [84]. It is also suggested that DNA-binding proteins of mitochondrial nucleoids can be as equally protective as histones for mtDNA under H 2 O 2 or X-ray exposure [85,86].…”

Section: Mtdna Characteristicsmentioning

confidence: 95%

How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models

Gisbergen

Voets

Starmans

et al. 2015

Mutation Research/Reviews in Mutation Research

166

151

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Several mutations in nuclear genes encoding for mitochondrial components have been associated with an increased cancer risk or are even causative, e.g. succinate dehydrogenase (SDHB, SDHC and SDHD genes) and iso-citrate dehydrogenase (IDH1 and IDH2 genes). Recently, studies have suggested an eminent role for mitochondrial DNA (mtDNA) mutations in the development of a wide variety of cancers. Various studies associated mtDNA abnormalities, including mutations, deletions, inversions and copy number alterations, with mitochondrial dysfunction. This might, explain the hampered cellular bioenergetics in many cancer cell types. Germline (e.g. m.10398A>G; m.6253T>C) and somatic mtDNA mutations as well as differences in mtDNA copy number seem to be associated with cancer risk. It seems that mtDNA can contribute as driver or as complementary gene mutation according to the multiple-hit model. This can enhance the mutagenic/clonogenic potential of the cell as observed for m.8993T>G or influences the metastatic potential in later stages of cancer progression. Alternatively, other mtDNA variations will be innocent passenger mutations in a tumor and therefore do not contribute to the tumorigenic or metastatic potential. In this review, we discuss how reported mtDNA variations interfere with cancer treatment and what implications this has on current successful pharmaceutical interventions. Mutations in MT-ND4 and mtDNA depletion have been reported to be involved in cisplatin resistance. Pharmaceutical impairment of OXPHOS by metformin can increase the efficiency of radiotherapy. To study mitochondrial dysfunction in cancer, different cellular models (like ρ(0) cells or cybrids), in vivo murine models (xenografts and specific mtDNA mouse models in combination with a spontaneous cancer mouse model) and small animal models (e.g. Danio rerio) could be potentially interesting to use. For future research, we foresee that unraveling mtDNA variations can contribute to personalized therapy for specific cancer types and improve the outcome of the disease.

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Section: Mtdna Characteristicsmentioning

confidence: 95%

How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models

Gisbergen

Voets

Starmans

et al. 2015

Mutation Research/Reviews in Mutation Research

166

151

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“…In contrast, the mitochondrial genome lacks histones, which has led to the belief that the observed high rate of mtDNA mutagenesis ( 10-fold greater than in nDNA) (Brown et al 1979;Ballard and Whitlock 2004;Tatarenkov and Avise 2007) is explained by the lack of "protective" histones. This belief lacks direct experimental support and remains controversial because it contradicts some experimental evidence, which suggests that histones, at least under some conditions, may enhance, rather than reduce DNA damage (Liang et al 1999;Liang and Dedon 2001), and that mtDNA-associated proteins may be at least as protective against mutagenic insults as histones under other conditions (Guliaeva et al 2006;Alexeyev 2009). Moreover, mtDNA may be physically covered with TFAM, an HMG-like protein involved in mtDNA transcription and replication.…”

mentioning

confidence: 88%

The Maintenance of Mitochondrial DNA Integrity--Critical Analysis and Update

Alexeyev

Shokolenko

Wilson

et al. 2013

Cold Spring Harbor Perspectives in Biology

361

342

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DNA molecules in mitochondria, just like those in the nucleus of eukaryotic cells, are constantly damaged by noxious agents. Eukaryotic cells have developed efficient mechanisms to deal with this assault. The process of DNA repair in mitochondria, initially believed nonexistent, has now evolved into a mature area of research. In recent years, it has become increasingly appreciated that mitochondria possess many of the same DNA repair pathways that the nucleus does. Moreover, a unique pathway that is enabled by high redundancy of the mitochondrial DNA and allows for the disposal of damaged DNA molecules operates in this organelle. In this review, we attempt to present a unified view of our current understanding of the process of DNA repair in mitochondria with an emphasis on issues that appear controversial.

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“…However, this view is being revised due to several recent discoveries. For example, mtDNA-binding proteins, and especially the mitochondrial transcription factor A (TFAM), offer some degree of protection [Alam et al, 2003;Guliaeva et al, 2006;Noack et al, 2006;Rebelo et al, 2009]. Regarding mtDNA repair, it seemed well established that mammalian mitochondria possess a proficient SP-BER pathway, which can efficiently repair many base lesions [Bogenhagen, 1999;Stierum et al, 1999].…”

Section: Introductionmentioning

confidence: 99%

DNA repair in mammalian mitochondria: Much more than we thought?

Liu

Demple

2010

Environ and Mol Mutagen

152

127

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For many years, the repair of most damage in mitochondrial DNA (mtDNA) was thought limited to short-patch base excision repair (SP-BER), which replaces a single nucleotide by the sequential action of DNA glycosylases, an apurinic/apyrimidinic (AP) endonuclease, the mitochondrial DNA polymerase gamma, an abasic lyase activity, and mitochondrial DNA ligase. However, the likely array of lesions inflicted on mtDNA by oxygen radicals and the possibility of replication errors and disruptions indicated that such a restricted repair repertoire would be inadequate. Recent studies have considerably expanded our knowledge of mtDNA repair to include long-patch base excision repair (LP-BER), mismatch repair, and homologous recombination and nonhomologous end-joining. In addition, elimination of mutagenic 8-oxodeoxyguanosine triphosphate (8-oxodGTP) helps prevent cell death due to the accumulation of this oxidation product in mtDNA. Although it was suspected for many years that irreparably damaged mtDNA might be targeted for degradation, only recently was clear evidence provided for this hypothesis. Therefore, multiple DNA repair pathways and controlled degradation of mtDNA function together to maintain the integrity of mitochondrial genome.

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Proteins associated with mitochondrial DNA protect it against X-rays and hydrogen peroxide

Cited by 20 publications

References 17 publications

How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models

How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models

The Maintenance of Mitochondrial DNA Integrity--Critical Analysis and Update

DNA repair in mammalian mitochondria: Much more than we thought?

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