FIGURE 4.

Transcription‐induced double‐strand break (DSB) and DNA breaks are associated with cancer development. (3.1) During transcriptional activation, R‐loops generated by transcriptional terminal sites or RNA polymerase II (RNAPII) pausing sites are resolved and repaired by senataxin (SETX) and breast cancer type 1 (BRCA1). (3.2) Furthermore, androgen receptor (AR)‐induced DSB at the promoter region by topoisomerase (DNA) II (TOP2) leads to oncogenic TMPRSS2‐ERG translocation. Estrogen receptor (ER) also induces DSBs at promoter regions by TOP2. Tyrosyl‐DNA phosphodiesterase 2 (TDP2) removes TOP2 covalently bound to DNA to repair cleavage via BRCA1‐mediated nonhomologous end‐joining (NHEJ). Loss of BRCA1 increases DSBs in TDP2‐knockout breast cancer cells, suggesting that it may suppress tumorigenesis in ER‐dependent tissues