Mutant SRSF2 and RUNX1 deficiency synergistically affect the DNA damage response and cell cycle. (A) GO enrichment cluster analysis of the dysregulated splicing events in double mutant (mt) cells compared with WT K562 cells. (B) Heatmap of the most significantly enriched GO categories of misspliced transcripts in each single/double mutant K562 genotype relative to WT K562 cells. (C) GO enrichment cluster analysis of the dysregulated splicing events in double mutant murine LK cells compared with WT cells. ClusterProfiler³³ was used to refine overlapping GOs by calculating enriched functional categories of individual gene clusters in panels A and C. The colors of the circles indicate the P values and the sizes of the circles indicate the number of genes in each GO term. (D) Heatmap of the most significantly enriched GO categories of misspliced transcripts in single and double mutant LK cells relative to WT cells. (E-H) Reverse transcription polymerase chain reaction validation and sashimi plots depicting the abnormal splicing of genes related to the DNA damage checkpoint (BRIP1), DNA repair (NABP1), and cell cycle (TBRG4 and AKAP8L). bp, base pair; mRNA, messenger RNA; RPKM, reads per kilo base per million mapped reads.