Intracellular Localization of 8-Oxo-dGTPase in Human Cells, with Special Reference to the Role of the Enzyme in Mitochondria

Kang, Dongchon; Nishida, Jun‐ichi; Iyama, Akihiro; Nakabeppu, Yusaku; Furuichi, Masayuki; Fujiwara, Toshiyuki; Sekiguchi, Mutsuo; Takeshige, Koichiro

doi:10.1074/jbc.270.24.14659

Cited by 183 publications

(140 citation statements)

References 39 publications

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“…Aburatani et al (1997) reported another isoform lacking NLS, in which exon 7 was replaced by exon 8 located at the downstream of exon 7. hOGG1 proteins without NLS are expected to have di erent intracellular localization. Recently, hMTH protein, a 8-hydroxydeoxyguanosine triphosphatase, was shown as being present in nucleus, mitochondria and cytosol (Kang et al, 1995). Therefore, each isoform of the hOGG1 proteins may have distinct intracellular localization and distinct functions in human cells.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA

Kohno¹,

Shinmura

Tosaka³

et al. 1998

Oncogene

388

309

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The hOGG1 gene encodes a DNA glycosylase that excises 8-hydroxyguanine (oh 8 Gua) from damaged DNA. Structural analyses of the hOGG1 gene and its transcripts were performed in normal and lung cancer cells. Due to a genetic polymorphism at codon 326, hOGG1-Ser 326 and hOGG1-Cys 326 proteins were produced in human cells. Activity in the repair of oh 8 Gua was greater in hOGG1-Ser 326 protein than in hOGG1-Cys 326 protein in the complementation assay of an E. coli mutant defective in the repair of oh 8 Gua. Two isoforms of hOGG1 transcripts produced by alternative splicing encoded distinct hOGG1 proteins: one with and the other without a putative nuclear localization signal. Loss of heterozygosity at the hOGG1 locus was frequently (15/ 23, 62.2%) detected in lung cancer cells, and a cell line NCI-H526 had a mutation leading to the formation of the transcripts encoding a truncated hOGG1 protein. However, the oh 8 Gua levels in nuclear DNA were similar among lung cancer cells and leukocytes irrespective of the type of hOGG1 proteins expressed. These results suggest that the oh 8 Gua levels are maintained at a steady level, even though multiple hOGG1 proteins are produced due to genetic polymorphisms, mutations and alternative splicing of the hOGG1 gene.

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Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA

Kohno¹,

Shinmura

Tosaka³

et al. 1998

Oncogene

388

309

View full text Add to dashboard Cite

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“…Mitochondria were isolated from mouse brain using a method modifi ed from Kang et al ( 70 ). In brief, 2 mouse brains were washed, minced in 5 ml of ice-cold Mito buff er (10 mM Tris HCl, pH 7.8, plus 0.2 mM EDTA, 0.25 M sucrose, and protease inhibitors), and homogenized.…”

Section: Methodsmentioning

confidence: 99%

MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

Kim¹,

Zhou²,

Qian³

et al. 2007

J Cell Biol

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“…Mitochondria of HeLa cells were prepared by differential centrifugation (9). Briefly, the cells suspended in buffer (TES) containing 0.25 M sucrose, 10 mM Tris-HCl, pH 7.4, and 0.1 mM EDTA were homogenized with a Potter-Elvehjem homogenizer and centrifuged at 600 ϫ g for 10 min at 4°C.…”

Section: Preparation Of Mitochondriamentioning

confidence: 99%

“…HeLa MRV11 and Jurkat (human T cell leukemia line) cells were cultured as described (9) and were harvested in logarithmic proliferation phase. The cells (about 10 6 cells) were centrifuged, and the pellets were rapidly denatured and solubilized in 100 l of denaturing buffer containing 50 mM Tris-HCl, pH 7.4, 1 mM EDTA, 1% SDS, and 0.1 mg/ml proteinase K at 50°C for 1 h. Total DNA was isolated by two extractions with phenol/chloroform (1/1), and then DNA was ethanol precipitated.…”

Section: Preparation Of Dnamentioning

confidence: 99%

In Vivo Determination of Replication Origins of Human Mitochondrial DNA by Ligation-mediated Polymerase Chain Reaction

Kang

Miyako

Kai

et al. 1997

Journal of Biological Chemistry

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A large part of replication is aborted in human mitochondria, the result being a D-loop. As few attempts have been made to distinguish free 5 ends of true replicate from those of abortive ones, we examined the 5 ends of true replicate of human mitochondrial DNA at one nucleotide resolution in vivo by making use of ligation-mediated polymerase chain reaction. The distribution and relative amounts of origins of the true replicate are exactly the same as those of total newly synthesized heavy strands, which means that the abortion of replication is independent of 5 ends. Treatment of DNA with RNase H frees 5 ends on both heavy and light strands. This is the first in vivo evidence for covalently attached primer RNA to nascent strand in human mitochondrial DNA.Replication of mitochondrial DNA (mtDNA) begins with synthesis of the heavy strand (H strand) 1 from the replication origin O H , following transcription of the light strand (L strand). Transcription of the L strand is regulated by the L strand promoter (LSP) sequence. When synthesis of the H strand has proceeded about two-thirds, synthesis of the L strand begins from replication origin O L . Thus, the total replication rate of mtDNA is determined by H strand synthesis (for reviews, see Refs. 1-3). The multiple replication origins of human mitochondrial H and L strands have been determined as free 5Ј ends of mtDNA extracted from prepared mitochondria. The molecular mechanism and physiological significance of these events are poorly understood.A large part of the synthesis of H strand is aborted, leaving a displacement loop ((D-loop) or 7 S DNA). For example, over 95% of the newly synthesized H strand is a D-loop in the case of mouse L cells (4). This makes it difficult to precisely determine origins of the true replication form (nascent H strand) (5). Few investigators have distinguished the free 5Ј end of the true replicate form from that of the D-loop even though selective detection of the free 5Ј end of the true replicate form is critical to determine replication origin. Although the 5Ј ends of the nascent H strand are suggested to be the same as those of D-loop in human mitochondria (5), it is uncertain whether the distribution and relative amount of the 5Ј ends of nascent H strand are exactly the same as those of the D-loop. In addition, the free 5Ј ends of human mtDNA are not set at one nucleotide resolution (6). To precisely determine the replication origin but not the simple free 5Ј end, it is required to selectively detect the replication origin at a higher resolution.We made use of the ligation-mediated polymerase chain reaction (LMPCR) to detect free 5Ј ends (7,8), an approach which makes feasible use of total DNA extracted directly from whole cells. By selective amplification of nascent H (not D-loop), we determined precise and comprehensive replication origins of the H strand in vivo. Here, we describe sites of free 5Ј ends and the transition sites of RNA to DNA for both H and L strands at one nucleotide resolution.

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Intracellular Localization of 8-Oxo-dGTPase in Human Cells, with Special Reference to the Role of the Enzyme in Mitochondria

Cited by 183 publications

References 39 publications

Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA

Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA

MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

In Vivo Determination of Replication Origins of Human Mitochondrial DNA by Ligation-mediated Polymerase Chain Reaction

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