Extended Data Figure 8: Translocations to AID off-targets are increased by idelalisib and duvelisib treatment in MEC1 and JeKo-1 cell line.
From: Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells
a, b, Distribution of translocation junctions in the IGH locus (a) and in the IRF4 AID off-target gene (b) in MEC1 cells. AID-knockout MEC1 cells were generated by CRISPR/Cas9-mediated deletion. Numbers of translocation junctions in focal clusters are indicated in bold. c, Translocation junction frequency in AID on-target and AID off-target sites in JeKo-1 B-cell line treated with DMSO, idelalisib or duvelisib (1 μM). Data are from pooled HTGTS libraries of similar size (Supplementary Tables 1, 4) from 3 independent experiments. Statistical analysis in Methods. *FDR ≤ 0.1, **FDR ≤ 0.01. d, Distribution of translocation junctions in the PIM1 AID off-target gene in JeKo-1 B-cell line. Numbers of translocation junctions in focal clusters are indicated in bold. e, AID-knockout MEC1 cells were generated by CRISPR/Cas9-mediated deletion, cloned and validated by indel sequencing of the Cas9 target site and by AID protein expression. Western blot for AID showing the parental cells (wild type), two AID-knockout clones (4 and 10) and one AID wild-type clone (6). AID-knockout clone 4 was treated with 1 μM DMSO, idelalisib or duvelisib (right panel) (n = 2 biological replicates). For gel source data, see Supplementary Fig. 1.
