10.17632/9W4G54BV43.1
Harrington, Lea
Lea
Harrington
Genome-wide screens reveal that resveratrol induces replicative stress in human cells
Mendeley
2020
Dataset
DNA Replication
High-Throughput Screening
High-Throughput Sequencing
Benslimane, Yahya
Yahya
Benslimane
Bertomeu, Thierry
Thierry
Bertomeu
Coulombe-Huntington, Jasmin
Jasmin
Coulombe-Huntington
McQuaid, Mary
Mary
McQuaid
Sánchez-Osuna, María
María
Sánchez-Osuna
Papadopoli, David
David
Papadopoli
Avizonis, Daina
Daina
Avizonis
De Sa Tavares Russo, Mariana
Mariana
De Sa Tavares Russo
Huard, Caroline
Caroline
Huard
Topisirovic, Ivan
Ivan
Topisirovic
Wurtele, Hugo
Hugo
Wurtele
Tyers, Mike
Mike
Tyers
2020-08-04
10.17632/9w4g54bv43
Creative Commons Attribution 4.0 International
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.