The splicing factor XAB2 interacts with ERCC1-XPF and XPG for R-loop processing

Abstract RNA splicing, transcription and the DNA damage response are intriguingly linked in mammals but underlying mechanisms remain poorly understood. Using an vivo biotinylation tagging approach mice, we show that splicing factor XAB2 interacts with core spliceosome it binds to spliceosomal U4 U6 snRNAs pre-mRNAs developing livers. depletion leads aberrant intron retention, R-loop formation cells. Studies illudin S-treated cells Csb m/m livers reveal transcription-blocking lesions trigger release of from all targets tested. Immunoprecipitation studies ERCC1-XPF XPG endonucleases outside nucleotide excision repair trimeric protein complex RNA:DNA hybrids under conditions favor R-loops. Thus, functionally links processing important ramifications for transcription-coupled disorders.