Article
Functional interrogation of DNA damage response variants with base editing screens.
Cell - 18 Feb 2021
Cuella-Martin Raquel, Hayward Samuel B, Fan Xiao, Chen Xiao, Huang Jen-Wei, Taglialatela Angelo, Leuzzi Giuseppe, Zhao Junfei, Rabadan Raul, Lu Chao, Shen Yufeng, Ciccia Alberto
Abstract excerpt
Mutations in DNA damage response (DDR) genes endanger genome integrity and predispose to cancer and genetic disorders. Here, using CRISPR-dependent cytosine base editing screens, we identify > 2,000 sgRNAs that generate nucleotide variants in 86 DDR genes, resulting in altered cellular fitness upon DNA damage. Among those variants, we discover loss- and gain-of-function mutants in the Tudor domain of the DDR...
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