DNA Degradation and Its Defects

Kawane, Kohki; Motani, Kou; Nagata, Shinji

doi:10.1101/cshperspect.a016394

Cited by 80 publications

(50 citation statements)

References 113 publications

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“…Enzymatic mechanisms for removal of DNA methylation may release repaired products into the bloodstream and consequently they can appear in the urine. In fact, the deoxynucleosides of 5mC and 5hmC –namely 5-methyl-2-deoxycytidine (5mdC) and 5-hydroxymethyl-2-deoxycytidine (5hmdC)– have recently been detected and quantified in urine3536, and several biological processes such as apoptosis can degrade DNA into single deoxynucleosides37. According to these studies, urinary 5mdC and 5hmdC contents may offer a view of the metabolic and functional status of tissues or organs in the human body.…”

Section: Resultsmentioning

confidence: 99%

Prostate Cancer Patients–Negative Biopsy Controls Discrimination by Untargeted Metabolomics Analysis of Urine by LC-QTOF: Upstream Information on Other Omics

Fernández-Peralbo

Gómez

Calderón-Santiago

et al. 2016

Sci Rep

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The existing clinical biomarkers for prostate cancer (PCa) diagnosis are far from ideal (e.g., the prostate specific antigen (PSA) serum level suffers from lack of specificity, providing frequent false positives leading to over-diagnosis). A key step in the search for minimum invasive tests to complement or replace PSA should be supported on the changes experienced by the biochemical pathways in PCa patients as compared to negative biopsy control individuals. In this research a comprehensive global analysis by LC–QTOF was applied to urine from 62 patients with a clinically significant PCa and 42 healthy individuals, both groups confirmed by biopsy. An unpaired t-test (p-value < 0.05) provided 28 significant metabolites tentatively identified in urine, used to develop a partial least squares discriminant analysis (PLS-DA) model characterized by 88.4 and 92.9% of sensitivity and specificity, respectively. Among the 28 significant metabolites 27 were present at lower concentrations in PCa patients than in control individuals, while only one reported higher concentrations in PCa patients. The connection among the biochemical pathways in which they are involved (DNA methylation, epigenetic marks on histones and RNA cap methylation) could explain the concentration changes with PCa and supports, once again, the role of metabolomics in upstream processes.

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Section: Resultsmentioning

confidence: 99%

Prostate Cancer Patients–Negative Biopsy Controls Discrimination by Untargeted Metabolomics Analysis of Urine by LC-QTOF: Upstream Information on Other Omics

Fernández-Peralbo

Gómez

Calderón-Santiago

et al. 2016

Sci Rep

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“…The biological mechanism for the interference of phthalates with urinary 5mdC and 5hmdC is unclear. Urinary 5mdC and 5hmdC may be the degradation products of genomic DNA metabolism (e.g., DNA degradation, DNA excise repair), which could be affected by several processes such as apoptosis or DNA damage (Kawane et al, 2014;Nagata et al, 2003). Previous research showed that phthalate exposure increased the production of reactive oxygen species (Rusyn et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Several biological processes, such as apoptosis, can cause DNA to degrade into single deoxynucleosides (Kawane et al, 2014;Nagata et al, 2003). It is hypothesized that urinary 5mdC and 5hmdC molecules may result from metabolism of methylated DNA (e.g., DNA degradation or DNA excision repair) (Hu et al, 2012;Yin et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Associations of urinary 5-methyl-2′-deoxycytidine and 5-hydroxymethyl-2′-deoxycytidine with phthalate exposure and semen quality in 562 Chinese adult men

Pan

Jing

Yeung

et al. 2016

Environment International

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“…4B). G4DNA structures from damaged G-rich sequences provide a direct mechanism for the cell to sense oxidative stress-induced DNA damage (56). The formation of stress granules is known to modulate RNA translation during oxidative stress (24,57).…”

Section: Discussionmentioning

confidence: 99%

Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress

Byrd¹,

Zybailov

Maddukuri³

et al. 2016

Journal of Biological Chemistry

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Cells engage numerous signaling pathways in response to oxidative stress that together repair macromolecular damage or direct the cell toward apoptosis. As a result of DNA damage, mitochondrial DNA or nuclear DNA has been shown to enter the cytoplasm where it binds to "DNA sensors," which in turn initiate signaling cascades. Here we report data that support a novel signaling pathway in response to oxidative stress mediated by specific guanine-rich sequences that can fold into G-quadruplex DNA (G4DNA). In response to oxidative stress, we demonstrate that sequences capable of forming G4DNA appear at increasing levels in the cytoplasm and participate in assembly of stress granules. Identified proteins that bind to endogenous G4DNA in the cytoplasm are known to modulate mRNA translation and participate in stress granule formation. Consistent with these findings, stress granule formation is known to regulate mRNA translation during oxidative stress. We propose a signaling pathway whereby cells can rapidly respond to DNA damage caused by oxidative stress. Guanine-rich sequences that are excised from damaged genomic DNA are proposed to enter the cytoplasm where they can regulate translation through stress granule formation. This newly proposed role for G4DNA provides an additional molecular explanation for why such sequences are prevalent in the human genome.

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DNA Degradation and Its Defects

Cited by 80 publications

References 113 publications

Prostate Cancer Patients–Negative Biopsy Controls Discrimination by Untargeted Metabolomics Analysis of Urine by LC-QTOF: Upstream Information on Other Omics

Prostate Cancer Patients–Negative Biopsy Controls Discrimination by Untargeted Metabolomics Analysis of Urine by LC-QTOF: Upstream Information on Other Omics

Associations of urinary 5-methyl-2′-deoxycytidine and 5-hydroxymethyl-2′-deoxycytidine with phthalate exposure and semen quality in 562 Chinese adult men

Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress

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