DNA topoisomerase 3-beta-1 (TOP3B)

DNA topoisomerase 3-beta-1 (TOP3B) is a unique metazoan enzyme in the type IA family, notable for its ability to act on both DNA and RNA substrates. It resolves DNA/RNA topological entanglements—unknotting, decatenating, and resolving supercoils—by transiently breaking and rejoining single-stranded DNA or RNA, permitting the passage of another strand. Unlike most topoisomerases, TOP3B also participates robustly in RNA metabolism, including the disassembly of R-loops, regulation of mRNA translation, and association with the scaffold protein TDRD3 (which recruits TOP3B to specific chromatin or RNA sites). Its physiological importance in genome stability, neurodevelopment, and aging is well established. Mutations in TOP3B are linked to neurodevelopmental disorders, and its diverse nucleic acid substrate recognition makes it an emerging target for antiviral and anticancer drug discovery.

Other names

DNA topoisomerase III betaTOP3BTOP3B1topoisomerase (DNA) III betaDNA topoisomerase 3-beta-1DNA topoisomerase III beta-1topoisomerase III beta

For theoretical/topoisomerase-directed small molecules: Inhibition of TOP3B would block relaxation of DNA/RNA structures, increase accumulation of R-loops and/or DNA damage, leading to cytostatic or cytotoxic effects (extrapolated from general topoisomerase mechanisms)