The Establishment of an Assay to Measure DNA Polymerase-Catalyzed Repair of UVB-Induced DNA Damage in Skin Cells and Screening of DNA Polymerase Enhancers from Medicinal Plants

Ikeoka, Sawako; Nakahara, Tsutomu; Iwahashi, Hiroyasu; Mizushina, Yoshiyuki

doi:10.3390/ijms17050667

Cited by 7 publications

(5 citation statements)

References 27 publications

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“…For example, DNA damage can be prevented by certain molecules, especially natural antioxidant compounds such as flavonoids, polyphenols, and carotenoids, which exist in fruits, vegetables, and medicinal plants. [17][18][19][20][21][22] Screening for highly effective, non-toxic, antioxidant compounds that protect against DNA damage is now an active area of biomedical research [23] , and interest in this area is growing. Various natural antioxidants have been successfully isolated from plants, such as rutin, resveratrol, and various flavonoids.…”

Section: Introductionmentioning

confidence: 99%

DNA protection activity of a hydroethanol extract and six polyphenol monomers fromMorus alba L. (mulberry) twig

Jia

et al. 2017

International Journal of Food Properties

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Morus alba L. (mulberry) is one of the most important medicine and food crops in China and other developing countries in Asia due to its large biomass (twigs) and useful by-products. Additionally, its twigs are an excellent green resource for bioactive compounds that are resistant to ultraviolet (UV) radiation and that can whiten skin and scavenge free radicals, and are of potential interest to the cosmetics and health food industries. In this study, we evaluated the ability of Morus alba L. twig hydroethanol extract and isolated compounds to protect DNA against UV damage. Agarose gel electrophoresis showed that a hydroethanol extract and six different polyphenol monomers (oxyresveratrol, resveratrol, mulberroside A, rutin, quercetin, and morin) present in the extract protected pUC19 plasmid DNA from UV damage. The optimal concentrations of polyphenols and Morus alba L. twig extract for DNA protection were 0.500 mg/mL and 1.00 mg/mL, respectively. These compounds may have potential as skin-care products to prevent UV-induced damage to the skin. Additionally, activity contribution degree assessment revealed other Morus alba L. substances possessing significant DNA protection activity that are worthy of further investigation. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

DNA protection activity of a hydroethanol extract and six polyphenol monomers fromMorus alba L. (mulberry) twig

Jia

et al. 2017

International Journal of Food Properties

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“…1 indicate that damaged mitochondria remained in cells at 24 h after exposure to more than 40 mJ／cm 2 of UV-B, suggesting that the dose of UV-B had an impact on mitophagy in NHEKs. Additionally, a previous study 6 indicated that the inherent cellular DNA repair system peaked at 4 h after UV-B irradiation.…”

Section: Mitophagy In Uv-b-irradiated Nheksmentioning

confidence: 93%

“…We assumed that it is effective to enhance the inherent repair ability of cells by promoting activity of cellular pol which synthesizes DNA strands in the repair system. In previous studies 5 , 6 , we established a method for measuring pol activity in UV-B-irradiated normal human epidermal keratinocytes NHEKs , and found that the inherent cellular DNA repair activity peaked at 4 h after irradiation with UV-B in NHEKs. We also showed that Rhodomyrtus tomentosa fruit extract, which has properties to protect epidermal keratinocytes from UV-B-induced apoptosis 7 , enhanced the cellular pol activity and suppressed CPD production.…”

Section: Introductionmentioning

confidence: 99%

The Involvement of Mitophagy in the Prevention of UV-B-Induced Damage in Human Epidermal Keratinocytes

Ikeoka¹,

Kiso²

2020

Jouranal of Society Cosmetic Chemists Japan

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Human skin is influenced by ultraviolet-B UV-B irradiation. UV-B induces DNA damage and mitochondrial damage in epidermal keratinocytes then accumulation of excessive DNA damage and damaged mitochondria finally leads to apoptosis. Recently, we investigated effective means to repair or to eliminate fatal damage leading to excessive apoptosis in UV-B-exposed normal human epidermal keratinocytes NHEKs Concerning repair of DNA damage, we previously established a method for measuring activity of cellular DNA polymerase pol which synthesizes DNA strands in the repair system in NHEKs, and found that Rhodomyrtus tomentosa fruit extract, which has properties to protect epidermal keratinocytes from UV-B-induced apoptosis, enhanced activity of pol in UV-B-irradiated NHEKs. With regard to repair and elimination of mitochondrial damage, we focused on mitophagy, which is the cellular function to remove dysfunctional mitochondria by autophagy. In the present study, we detected mitophagy and evaluated mitochondrial reductase activity providing an indication of cell viability in UV-B-irradiated NHEKs. As a result of evaluating the influence of UV-B irradiation on mitophagy in NHEKs, we observed that mitophagy became weak after irradiation with 40 mJ／cm 2 UV-B. In addition, mitochondrial reductase activity also decreased at 24 h after irradiation. Following these results, we also found that Rhodomyrtus tomentosa fruit extract suppressed the UV-B-induced decrease in mitophagy and in mitochondrial reductase activity. Furthermore, we investigated influence of UV-B irradiation and effect of the extract on mitochondrial membrane potential in NHEKs to elucidate the mechanisms of modulating mitophagy. The results showed that the extract retained normal function of mitophagy by decreasing mitochondrial membrane potential in advance. In conclusion, it was suggested that the enhancement of inherent cellular DNA repair properties and the efficient elimination of the mitochondrial damage are essential for protecting the epidermal keratinocytes from UV-B-induced excessive apoptosis.

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“…Mammalian cells are known to contain at least 16 different DNA polymerases that function in semiconservative DNA replication (pols α, δ, ε), base excision repair (pol β), mitochondrial DNA replication, repair and degradation (pol γ), DSB repair and immunological diversity (pols λ, μ, pol θ, and terminal deoxynucleotidyl transferase), and DNA damage tolerance by translesion synthesis [ 8 ]. Among them, DNA polymerase theta has the most unique structure.…”

Section: Polθ: Structure and Functionsmentioning

confidence: 99%

“…In recent research, inhibiting Pol was found to sensitize cells to replication stress produced by drugs such as topoisomerase poisons or ATR inhibitors, leading to new cancer treatment candidates. DSB repair-proficient cancer cells expressing high levels of Polθ may be sensitive to the inhibition of Polθ in combination with standard cytotoxic drugs [ 8 ].…”

Section: The Role Of Polθ In Malignant Cellsmentioning

confidence: 99%

Synthetic Lethality Targeting Polθ

Drzewiecka

Barszczewska-Pietraszek

Czarny

et al. 2022

Genes

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Research studies regarding synthetic lethality (SL) in human cells are primarily motivated by the potential of this phenomenon to be an effective, but at the same time, safe to the patient’s anti-cancer chemotherapy. Among the factors that are targets for the induction of the synthetic lethality effect, those involved in DNA repair seem to be the most relevant. Specifically, when mutation in one of the canonical DNA double-strand break (DSB) repair pathways occurs, which is a frequent event in cancer cells, the alternative pathways may be a promising target for the elimination of abnormal cells. Currently, inhibiting RAD52 and/or PARP1 in the tumor cells that are deficient in the canonical repair pathways has been the potential target for inducing the effect of synthetic lethality. Unfortunately, the development of resistance to commonly used PARP1 inhibitors (PARPi) represents the greatest obstacle to working out a successful treatment protocol. DNA polymerase theta (Polθ), encoded by the POLQ gene, plays a key role in an alternative DSB repair pathway—theta-mediated end joining (TMEJ). Thus, it is a promising target in the treatment of tumors harboring deficiencies in homologous recombination repair (HRR), where its inhibition can induce SL. In this review, the authors discuss the current state of knowledge on Polθ as a potential target for synthetic lethality-based anticancer therapies.

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The Establishment of an Assay to Measure DNA Polymerase-Catalyzed Repair of UVB-Induced DNA Damage in Skin Cells and Screening of DNA Polymerase Enhancers from Medicinal Plants

Cited by 7 publications

References 27 publications

DNA protection activity of a hydroethanol extract and six polyphenol monomers fromMorus alba L. (mulberry) twig

DNA protection activity of a hydroethanol extract and six polyphenol monomers fromMorus alba L. (mulberry) twig

The Involvement of Mitophagy in the Prevention of UV-B-Induced Damage in Human Epidermal Keratinocytes

Synthetic Lethality Targeting Polθ

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