DNA repair
How ubiquitin activates SPRTN to protect genome stability
21.07.2025
Julian Stingele's team uncovers how ubiquitin activates SPRTN to repair toxic DNA-protein crosslinks - a key mechanism for maintaining genome instability
SPRTN is a DNA repair enzyme that safeguards genome stability by removing toxic DNA-protein crosslinks (DPCs). Sophie Dürauer, a PhD student in Julian Stingele’s team, together with many collaborators discovered that ubiquitin plays a key role in activating SPRTN by binding directly to its protease domain. This interaction triggers a conformational change that switches SPRTN into its active state, ensuring that DNA repair occurs precisely when and where needed. Mutations that impair this activation mechanism lead to genomic instability. These findings reveal a critical regulatory mechanism governing DNA repair in human cells.
Original Publication:
Allosteric activation of the SPRTN protease by ubiquitin maintains genome stability
Dürauer S, Kang HS, Wiebeler C, Machida Y, Schnapka DS, Yaneva D, Renz C, Götz MJ, Weickert P, Major AC, Rahmanto AS, Gutenthaler-Tietze SM, Daumann LJ, Beli P, Ulrich HD, Sattler M, Machida YJ, Schwierz N, Stingele J.
Nature Communications 2025 https://doi.org/10.1038/s41467-025-61224-z