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. 2022 Feb 9;13:760. doi: 10.1038/s41467-022-28442-1

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Genetic screen in 32 HAP1 isogenic knockout cell lines covering different DNA damage repair pathways, as well as their wild-type (WT) counterpart. Efficiency of installation of a five base pair (bp) deletion in the HEK3 locus, using PE2 for n = 2 biologically independent experiments. Each radial line represents an increment of 1%. b PE2 of a 5 bp deletion in the HEK3 locus in the indicated mismatch repair-deficient cell lines (MMR−), and their respective complemented counterparts (MMR+). For each cell line, the mutated MMR genes are represented. Editing efficiency measured for n = 3 biologically independent experiments (with technical replicates also depicted). c Percentage of indels after a 5 bp deletion in the HEK3 locus using PE2 in varying mismatch repair-deficient (MMR−), and their respective complemented, cell lines (MMR+), for n = 3 biologically independent experiments (with technical replicates also depicted). For each cell line, the correspondent mutated MMR gene is indicated. d PE2 of the indicated types of edits (RNF2 locus) in HEK293 cells wild-type (MMR+), or knockout for MLH1 (MMR−). Values correspond to editing efficiency, measured for n = 3 biologically independent experiments. e Efficiency of PE2, PE3, and PE3b after inducing A>C or G>T mutations in the FANCF locus. HEK293 wild-type (MMR+) and MLH1 knockout cells (MMR−) were used. Editing efficiency for n = 3 biologically independent experiments. f PE3 efficiency of a 5 bp deletion in the HEK3 locus in RPE1 wild-type (WT) cells and an isogenic knockout MLH1 cell line (RPE1-MLH1^−/−), determined by Sanger sequencing and TIDE analysis, for n = 3 biologically independent experiments (technical replicates also depicted). RPE1 cells express Cas9(H840A)-RT in a constitutive manner (RPE1 PE2-BSD). g PE3 efficiency in wild-type (WT) human induced-pluripotent stem cells (hiPSCs), and isogenic knockouts for MLH1 and MSH2 (MLH1^−/−, MSH2^−/−), for n = 3 biologically independent experiments (technical replicates also depicted). Statistical analysis performed using unpaired two-tailed Student’s t-test across biological replicates only. Error bars reflect mean ± s.e.m. Source data are provided as a Source Data file.