Tudor domain-containing protein 3 (TDRD3), a multidomain scaffold protein functions as an epigenetic reader on nuclear chromatin and binds with fragile X mental retardation protein on mRNA. It forms a conserved complex with topoisomerase 3β (Top3β), a type IA topoisomerase, and participates in both transcription and translation. The mechanism of how TDRD3 acts as Top3β’s partner in regulating these cellular processes is unknown. Here, we demonstrated that TDRD3 is able to stimulate Top3β’s DNA and RNA topoisomerase catalytic activities, through binding and stabilizing single-stranded regions in DNA and RNA substrates. Because these regions are the preferred site for Top3β, TDRD3 acts as a regulator to provide access of the enzyme to these nucleic acid substrates and to act upon them. Read more