Because E2-dependent R-loop generation and rearrangement in breast cancer cells are mainly enriched at E2-responsive genomic loci, it is possible that Thrap3 might be localized to E2-responsive genomic loci with ERα and that this localization is followed by DDX5 recruitment for precise removal of cotranscriptional R-loops in breast cancer cells, which is critical for cancer progression. The gene discussed is ESR1; the disease is cancer.