Extended Data Fig. 3: RAD21 depletion in K562 cells leads to recurrent breaks on cancer-related genes.

a Flow diagram for the identification of translocation hotspot genes. See Methods for details. b Circos plots showing the genome-wide translocations and translocation hotspot genes cloned from the TP53 locus with RAD21 depletion. Legends are depicted as described in Fig. 2a. c Translocation frequencies of RAD21-depletion-induced translocation hotspot genes in RAD21-mAC 4# captured by MYC DSBs or RAD21-mAC 1# and 4# captured by TP53 DSBs. Legends are depicted as described in Fig. 2b. d Circos plots exhibiting the distribution of genome-wide DSBs in IAA-treated WT and RAD21-mAC cells. Histogram exhibits genome-wide DNA breaks with 1-Mb bin size and with a minimum of 10 in the log scale. Numbers in the circos plots represent the relative levels of DSBs in comparison to that of WT. e Representative profile of END-seq-captured DNA breaks on the BCR gene. The number of breaks was normalized to the same number of spike-in DSBs. See Methods for details. f The permutation test of PEM-seq-captured hotspot genes and fusion genes annotated in the Atlas of Genetics and Cytogenetics in Oncology and Haematology database. The red line indicates the overlapped number (N_real) between hotspot genes and fusion genes. Histograms show the distribution of overlapped numbers between hotspot genes and randomized genes from 1000 draws. The black dashed line indicates the upper bound of 95% confidence interval of the simulation. N_null indicates the mean value of the simulation. See Methods for details. g Mutation frequency of PEM-seq-identified translocation hotspot genes in the non-small cell lung cancer (top), glioma (middle), and colorectal cancer (bottom) patients with (red bars) or without (black bars) cohesin mutations. Legends are depicted as described in Fig. 2d. The genes on the left side of the dashed lines have p-values < 0.05 with the two-sided Chi-square test for independence of cohesin mutations.