{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang W"],"funding":["Shuguang Program\" of Shanghai Education Development Foundation and Shanghai Municipal Education Commission\"","Program of Shanghai Academic Research Leader","the Young Elite Scientist Sponsorship Program by CAST","National Science Foundation of China","Shanghai Rising-Star Program","the Fundamental Research Funds for the Central Universities, Program of Shanghai Academic Research Leader","The Young Elite Scientist Sponsorship Program by CAST","The key project of the Science and Technology of Shanghai Municipality","Fundamental Research Funds for the Central Universities","the key project of the Science and Technology of Shanghai Municipality","Shanghai Municipal Medical and Health Discipline Construction Projects",""Shuguang Program" of Shanghai Education Development Foundation and Shanghai Municipal Education Commission","the Shanghai Municipal Medical and Health Discipline Construction Projects","the Shanghai Rising-Star Program","\"Shuguang Program\" of Shanghai Education Development Foundation and Shanghai Municipal Education Commission","the National Science Foundation of China","Chinese National Program on Key Basic Research Project"],"pagination":["e56008"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7380943"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9"],"pubmed_abstract":["Directly modulating the choice between homologous recombination (HR) and non-homologous end joining (NHEJ) - two independent pathways for repairing DNA double-strand breaks (DSBs) - has the potential to improve the efficiency of gene targeting by CRISPR/Cas9. Here, we have developed a rapid and easy-to-score screening approach for identifying small molecules that affect the choice between the two DSB repair pathways. Using this tool, we identified a small molecule, farrerol, that promotes HR but does not affect NHEJ. Further mechanistic studies indicate that farrerol functions through stimulating the recruitment of RAD51 to DSB sites. Importantly, we demonstrated that farrerol effectively promotes precise targeted integration in human cells, mouse cells and mouse embryos at multiple genomic loci. In addition, treating cells with farrerol did not have any obvious negative effect on genomic stability. Moreover, farrerol significantly improved the knock-in efficiency in blastocysts, and the subsequently generated knock-in mice retained the capacity for germline transmission."],"journal":["eLife"],"pubmed_title":["A high-throughput small molecule screen identifies farrerol as a potentiator of CRISPR/Cas9-mediated genome editing."],"pmcid":["PMC7380943"],"funding_grant_id":["19JC1415300","19SG18","31721003","2017ZZ02015","2017YFA010330","2017YFA0103300","2016YFA0100400","81972457","2018YFC2000100","19QA1409600","19XD1403000","31871446","2018QNRC001","31871438"],"pubmed_authors":["Yang J","Zhang J","Chen J","Wan X","Yu J","Zhao X","Zhang W","Wang M","Jiang Y","Chen Y","Xu X","Gao S","Wei K","Mao Z"],"additional_accession":[]},"is_claimable":false,"name":"A high-throughput small molecule screen identifies farrerol as a potentiator of CRISPR/Cas9-mediated genome editing.","description":"Directly modulating the choice between homologous recombination (HR) and non-homologous end joining (NHEJ) - two independent pathways for repairing DNA double-strand breaks (DSBs) - has the potential to improve the efficiency of gene targeting by CRISPR/Cas9. Here, we have developed a rapid and easy-to-score screening approach for identifying small molecules that affect the choice between the two DSB repair pathways. Using this tool, we identified a small molecule, farrerol, that promotes HR but does not affect NHEJ. Further mechanistic studies indicate that farrerol functions through stimulating the recruitment of RAD51 to DSB sites. Importantly, we demonstrated that farrerol effectively promotes precise targeted integration in human cells, mouse cells and mouse embryos at multiple genomic loci. In addition, treating cells with farrerol did not have any obvious negative effect on genomic stability. Moreover, farrerol significantly improved the knock-in efficiency in blastocysts, and the subsequently generated knock-in mice retained the capacity for germline transmission.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jul","modification":"2026-05-02T20:28:19.869Z","creation":"2025-04-07T08:38:07.812Z"},"accession":"S-EPMC7380943","cross_references":{"pubmed":["32644042"],"doi":["10.7554/eLife.56008"]}}