Cellular forms of type IB topoisomerases distinguish themselves from their viral counterparts and the tyrosine recombinases to which they are closely related by having rather extensive N-terminal and linker domains. The functions and necessity of these domains are not yet fully unraveled. In this study we replace 86 amino acids including the linker domain of the cellular type IB topoisomerase, human topoisomerase I, with four, six, or eight amino acids from the corresponding short loop region in Cre recombinase. In vitro characterization of the resulting chimeras, denoted Cropos, reveals that six amino acids from the Cre linker loop constitute the minimal length of a functional linker in human topoisomerase I.