biostudies-literatureUnknownZhang HIntramural NIH HHSBoth transcription and replication can take place simultaneously on the same DNA template, potentially leading to transcription-replication conflicts (TRCs) and topological problems. Here we asked which topoisomerase(s) is/are the best candidate(s) for sensing TRC. Genome-wide topoisomerase binding sites were mapped in parallel for all the nuclear topoisomerases (TOP1, TOP2A, TOP2B, TOP3A and TOP3B). To increase the signal to noise ratio (SNR), we used ectopic expression of those topoisomerases in H293 cells followed by a modified CUT&Tag method. Although each topoisomerase showed distinct binding patterns, all topoisomerase binding signals positively correlated with gene transcription. TOP3A binding signals were suppressed by DNA replication inhibition. This was also observed but to a lesbioRxiv : the preprint server for biology2024.06.17.599352https://www.ebi.ac.uk/biostudies/studies/S-EPMC11212928biostudies-literatureGenome-wide Mapping of Topoisomerase Binding Sites Suggests Topoisomerase 3α (TOP3A) as a Reader of Transcription-Replication Conflicts (TRC).PMC11212928Z01 BC006150Saha SPommier YZhang HDhall ASaha LKPongor LSSun YfalseGenome-wide Mapping of Topoisomerase Binding Sites Suggests Topoisomerase 3α (TOP3A) as a Reader of Transcription-Replication Conflicts (TRC).Both transcription and replication can take place simultaneously on the same DNA template, potentially leading to transcription-replication conflicts (TRCs) and topological problems. Here we asked which topoisomerase(s) is/are the best candidate(s) for sensing TRC. Genome-wide topoisomerase binding sites were mapped in parallel for all the nuclear topoisomerases (TOP1, TOP2A, TOP2B, TOP3A and TOP3B). To increase the signal to noise ratio (SNR), we used ectopic expression of those topoisomerases in H293 cells followed by a modified CUT&Tag method. Although each topoisomerase showed distinct binding patterns, all topoisomerase binding signals positively correlated with gene transcription. TOP3A binding signals were suppressed by DNA replication inhibition. This was also observed but to a les2024-01-01T00:00:00Z2024 Jun2026-04-19T03:21:27.179Z2025-04-06T08:20:00.724ZS-EPMC112129283894881510.1101/2024.06.17.599352