Abstract
Dub gymnastics: allosteric regulation of deubiquitination
Ubiquitin conjugation attaches the small protein ubiquitin to other proteins. It changes the fate of a target protein by degradation, relocalisation or complex formation, leading to rewiring of cellular pathways These signals are balanced by deubiquitinating enzymes (DUBs), which antagonize ubiquitination of specific protein substrates. Because ubiquitination pathways are critically important, DUB activity is often carefully controlled.
We study DUB regulation, particularly in DNA repair. We use a combination of structural biology methods, ranging from X-ray crystallography and NMR to cryo-EM and AI, and combine this with quantitative biochemistry to provide understanding of allosteric regulation mechanisms.
Biography
Titia Sixma uses a combination of structural biology, biophysics and biochemistry to quantitatively analyze molecular mechanisms in cells. Her lab has a focus on mechanisms of ubiquitination in DNA regulation and DNA mismatch repair. She received her PhD in Groningen with Wim Hol and did her post-doc with Paul Sigler at Yale. She is group leader in the division of Biochemistry at the Netherlands Cancer Institute and ‘bijzonder hoogleraar’ at ErasmusMC (affiliated Professor). She is member of EMBO (2004), Academia Europaea (2008) and the Netherlands Academy KNAW. She received the NVBMB prize, an ERC advanced grant, several TOP research grants and is a member of the Oncode Institute.
