fig1

Figure 1. Schematic representation of the human TOP2α gene, TOP2α mRNAs, TOP2α protein, and visualization of RNA-seq results. A: the human TOP2α gene is comprised of 35 exons. At least three mature mRNA transcripts (i-iii) can be transcribed from the human TOP2α gene. Two of these mRNAs harbor retained and processed introns; B: the three TOP2α mRNAs encode three distinct TOP2α protein isoforms. Depicted are the ATP gate, which harbors the ATPase domain; the DNA gate, which includes the winged-helix domain and harbors the active site tyrosine, Tyr805; the C gate, which comprises the coiled-coil region (coiled domain) and the characterized dimerization sequences, DD1053-1069 and DD1121-1143^[41-45]; and the C-terminal domain, which contains the defined nuclear localization signal NLS1454-1497^[46,47]; C: visualization of retained intron 19 of TOP2α RNA-seq genome coverage tracks showing the intron 19 retention event in K/VP.5 cells. RNA-seq raw reads from K562 and K/VP.5 RNA samples were mapped to the human reference genome GRCh38 using Hierarchical Indexing for Spliced Alignment for Transcripts v.2.1.0^[48] and visualized using the Integrative Genomics Viewer^[49]. Reduced coverage denoted for Exon 20 indicates fewer full length TOP2α/170 reads in K/VP.5 cells. (A, B) Images adapted in part from Figures 1A, B published originally in the Journal of Pharmacology and Experimental Therapeutics; Kanagasabai et al.^[35], 2017. TOP2α: topoisomerase IIα; WHD: winged-helix domain; CTD: C-terminal domain; DD: dimerization domains