Genome-Wide Screens Reveal that Resveratrol Induces Replicative Stress in Human Cells.
Mol Cell
; 79(5): 846-856.e8, 2020 09 03.
Article
em En
| MEDLINE
| ID: mdl-32755594
ABSTRACT
Resveratrol is a natural product associated with wide-ranging effects in animal and cellular models, including lifespan extension. To identify the genetic target of resveratrol in human cells, we conducted genome-wide CRISPR-Cas9 screens to pinpoint genes that confer sensitivity or resistance to resveratrol. An extensive network of DNA damage response and replicative stress genes exhibited genetic interactions with resveratrol and its analog pterostilbene. These genetic profiles showed similarity to the response to hydroxyurea, an inhibitor of ribonucleotide reductase that causes replicative stress. Resveratrol, pterostilbene, and hydroxyurea caused similar depletion of nucleotide pools, inhibition of replication fork progression, and induction of replicative stress. The ability of resveratrol to inhibit cell proliferation and S phase transit was independent of the histone deacetylase sirtuin 1, which has been implicated in lifespan extension by resveratrol. These results establish that a primary impact of resveratrol on human cell proliferation is the induction of low-level replicative stress.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proliferação de Células
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Replicação do DNA
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Resveratrol
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article