Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability
Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability
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DOI：
10.1038/s41598-020-62292-5
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发表时间：
2020-03-25
影响因子：
4.6
通讯作者：
Yoshioka，Ken-ichi
中科院分区：
文献类型：
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作者：
Matsuno，Yusuke;Atsumi，Yuko;Yoshioka，Ken-ichi
基因组不稳定与突变的诱导有关，包括癌症驱动基因中的突变，以及随后具有废除的防御系统的细胞的克隆进化。当基因组稳定性维持时，不会诱导此类突变;然而，基因组稳定性维持所涉及的机制仍然难以捉摸。在这里，白藜芦醇（和相关的多酚）被证明可以增强小鼠胚胎成纤维细胞的基因组稳定性，最终保护细胞免受ARF/p53途径突变的诱导。复制应力相关的DNA双链断裂（DSB），积累与基因组不稳定有效地减少白藜芦醇治疗。此外，白藜芦醇暂时稳定组蛋白H2 AX的表达，这是参与DSB修复。对于相关多酚，观察到对维持基因组稳定性的类似作用。因此，我们提出多酚的摄入有助于抑制基因组不稳定性发展的癌症，以及延长寿命。
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.