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. 2022 Nov 2;8(44):eadd4920. doi: 10.1126/sciadv.add4920

Fig. 4. The roles of TOP2A, TOP2B, and TOP1 in RNA Pol II transcription regulation.

Fig. 4.

(A) The breaking model. TOP2B catalyzes DNA DSBs to promote permissive chromatin structures and facilitate RNA Pol II pause release for rapid activation of transcription. TOP1 removes DNA supercoils of elongating RNA Pol II via single-strand breaks (SSBs). (B) The nonbreaking model of transcriptional activation of immediate early genes (IEGs). Catalytic inhibition of TOP2A induces RNA Pol II promoter-proximal pause release independently of formation of DNA breaks. Negative supercoiling at TSS facilitates separation of DNA molecules, allowing tandem recruitment and transcription of multiple RNA Pol II complexes. Topological feedback loop of transcribing polymerases cancels negative and positive supercoiling. (C) Topoisomes assembled by MYC or MYCN transcription factors unite TOP1 and TOP2A or TOP2B, respectively. Topoisomes stimulate enzymatic activities of topoisomerases to overcome topological challenges resulting from high-output transcription of MYC/MYCN-regulated genes.