Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability

Yusuke Matsuno; Yuko Atsumi; Md Alauddin; Md Masud Rana; Haruka Fujimori; Mai Hyodo; Atsuhiro Shimizu; Tomoki Ikuta; Hiroko Tani; Hidetaka Torigoe; Yoshimichi Nakatsu; Teruhisa Tsuzuki; Michio Komai; Hitoshi Shirakawa; Ken ichi Yoshioka

doi:10.1038/s41598-020-62292-5

Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability

Yusuke Matsuno, Yuko Atsumi, Md Alauddin, Md Masud Rana, Haruka Fujimori, Mai Hyodo, Atsuhiro Shimizu, Tomoki Ikuta, Hiroko Tani, Hidetaka Torigoe, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Michio Komai, Hitoshi Shirakawa, Ken ichi Yoshioka

Bioregulation

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8 Citations (Scopus)

Abstract

Genomic destabilisation is associated with the induction of mutations, including those in cancer-driver genes, and subsequent clonal evolution of cells with abrogated defence systems. Such mutations are not induced when genome stability is maintained; however, the mechanisms involved in genome stability maintenance remain elusive. Here, resveratrol (and related polyphenols) is shown to enhance genome stability in mouse embryonic fibroblasts, ultimately protecting the cells against the induction of mutations in the ARF/p53 pathway. Replication stress-associated DNA double-strand breaks (DSBs) that accumulated with genomic destabilisation were effectively reduced by resveratrol treatment. In addition, resveratrol transiently stabilised the expression of histone H2AX, which is involved in DSB repair. Similar effects on the maintenance of genome stability were observed for related polyphenols. Accordingly, we propose that polyphenol consumption can contribute to the suppression of cancers that develop with genomic instability, as well as lifespan extension.

Original language	English
Article number	5388
Journal	Scientific reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-62292-5
Publication status	Published - Dec 1 2020

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Matsuno, Y., Atsumi, Y., Alauddin, M., Rana, M. M., Fujimori, H., Hyodo, M., Shimizu, A., Ikuta, T., Tani, H., Torigoe, H., Nakatsu, Y., Tsuzuki, T., Komai, M., Shirakawa, H., & Yoshioka, K. I. (2020). Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability. Scientific reports, 10(1), [5388]. https://doi.org/10.1038/s41598-020-62292-5

Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability. / Matsuno, Yusuke; Atsumi, Yuko; Alauddin, Md; Rana, Md Masud; Fujimori, Haruka; Hyodo, Mai; Shimizu, Atsuhiro; Ikuta, Tomoki; Tani, Hiroko; Torigoe, Hidetaka; Nakatsu, Yoshimichi; Tsuzuki, Teruhisa; Komai, Michio; Shirakawa, Hitoshi; Yoshioka, Ken ichi.

In: Scientific reports, Vol. 10, No. 1, 5388, 01.12.2020.

Research output: Contribution to journal › Article › peer-review

Matsuno, Yusuke ; Atsumi, Yuko ; Alauddin, Md ; Rana, Md Masud ; Fujimori, Haruka ; Hyodo, Mai ; Shimizu, Atsuhiro ; Ikuta, Tomoki ; Tani, Hiroko ; Torigoe, Hidetaka ; Nakatsu, Yoshimichi ; Tsuzuki, Teruhisa ; Komai, Michio ; Shirakawa, Hitoshi ; Yoshioka, Ken ichi. / Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability. In: Scientific reports. 2020 ; Vol. 10, No. 1.

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abstract = "Genomic destabilisation is associated with the induction of mutations, including those in cancer-driver genes, and subsequent clonal evolution of cells with abrogated defence systems. Such mutations are not induced when genome stability is maintained; however, the mechanisms involved in genome stability maintenance remain elusive. Here, resveratrol (and related polyphenols) is shown to enhance genome stability in mouse embryonic fibroblasts, ultimately protecting the cells against the induction of mutations in the ARF/p53 pathway. Replication stress-associated DNA double-strand breaks (DSBs) that accumulated with genomic destabilisation were effectively reduced by resveratrol treatment. In addition, resveratrol transiently stabilised the expression of histone H2AX, which is involved in DSB repair. Similar effects on the maintenance of genome stability were observed for related polyphenols. Accordingly, we propose that polyphenol consumption can contribute to the suppression of cancers that develop with genomic instability, as well as lifespan extension.",

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AU - Hyodo, Mai

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AU - Komai, Michio

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AU - Yoshioka, Ken ichi

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N2 - Genomic destabilisation is associated with the induction of mutations, including those in cancer-driver genes, and subsequent clonal evolution of cells with abrogated defence systems. Such mutations are not induced when genome stability is maintained; however, the mechanisms involved in genome stability maintenance remain elusive. Here, resveratrol (and related polyphenols) is shown to enhance genome stability in mouse embryonic fibroblasts, ultimately protecting the cells against the induction of mutations in the ARF/p53 pathway. Replication stress-associated DNA double-strand breaks (DSBs) that accumulated with genomic destabilisation were effectively reduced by resveratrol treatment. In addition, resveratrol transiently stabilised the expression of histone H2AX, which is involved in DSB repair. Similar effects on the maintenance of genome stability were observed for related polyphenols. Accordingly, we propose that polyphenol consumption can contribute to the suppression of cancers that develop with genomic instability, as well as lifespan extension.

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Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability

Abstract

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