New research sheds light on how transposases catalyze DNA rearrangement events.

A new publication in the journal Nature Communications by the group of Dr. Ernesto Arias at Centro de Investigaciones Biológicas Margarita Salas (CSIC) sheds light on how transposases catalyze DNA rearrangement events with broad impacts on gene expression, genome evolution, and drug resistance in bacteria. The study, the result of an international collaboration, focuses on IstA, a transposase present in the widespread IS21 family of mobile elements.

Transposons, a particular class of mobile genetic elements, are DNA sequences that have the ability to “jump” between different nucleic acid molecules. They often encode at least one protein, the transposase, which is the enzyme responsible for performing the strand-transfer reaction. Some transposable elements are used as biotechnological tools, whereas others are showing great potential in gene editing applications, and their DNA reshuffling activity has deep biological implications. More precisely, the IS21 family is found in most bacterial phyla, including numerous clinical and multidrug-resistant strains, and has played a key role in the evolution of human pathogens such as Yersinia pestis and Y. pseudotuberculosis.

Spínola-Amilibia et al. used biochemical and structural approaches to define how IstA engages the transposon terminal sequences to form a high-molecular-weight complex and promote DNA integration. Altogether, data demonstrate that IstA oligomerizes and associates with its cognate nucleic acid elements in a highly cooperative manner. High-resolution cryo-EM studies supported these observations and showed that the IS21 transposase forms a close-knit tetramer that engages the transposon ends with a remarkably intertwined configuration that can regulate the expression of the transposon-encoded proteins and neighboring host genes.

These findings provide insights into IS21 transposition and reveal how numerous transposases, including the highly-related Tn7 and bacteriophage Mu systems, may recognize the often-multiple terminal transposon repeats to prevent abnormal and deleterious double-strand breaks and facilitate efficient DNA reorganization events.

The study was conducted by the CIB group in collaboration with Prof. James Berger’s laboratory at Johns Hopkins University and it was funded by the Spanish Ministry of Science (PID2020-120275GB-I00 and BFU2017-89143-P funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”).

Reference: IS21 family transposase cleaved donor complex traps two right-handed superhelical crossings. Mercedes Spínola-Amilibia, Lidia Araújo-Bazán, Álvaro de la Gándara, James M. Berger, Ernesto Arias-Palomo (2023) Nature Commun. DOI: 0.1038/s41467-023-38071-x