Figure 3.

Model proposing that changes in alternative splicing triggered by mutations in SF3B1, SRSF2, and U2AF1 also occur through activation of the DDR. Drops in the activity or changes in the binding specificities of splicing factors alter splice site selection directly but are also proposed to promote the formation of R loops when segments of nascent pre-mRNAs are not adequately bound by splicing factors. R loop formation in turn triggers the DDR to elicit splicing changes in transcripts encoding DNA repair, chromatin structure, cell cycle and splicing control, and apoptotic components.