Abstract:

Enzymes from the base excision pathway such as uracil DNA-glycosylase (UDG) recognize and repair damaged DNA by flipping the lesion out of the helix stack. We have used computer simulations to show that DNA bending facilitates flipping, and that bendability is highly dependent on sequence. For UNG, the repair enzyme that removes the highly mutagenic uracil lesion from DNA, this coupling was shown to have significant effects on repair efficiencies, with higher excision rates for more flexible sequences. Our simulations also identified register-shifted structures, which sterically block re-entry of uracil into the helix stack and may facilitate damage recognition and repair. Inspired by the importance of conformational dynamics for DNA repair, we will also discuss new computational methods to treat the challenging and highly unusual conformational dynamics of metamorphic proteins.

Bio:

Professor Arjan van der Vaart received his MS in Biophysical Chemistry from the University of Groningen in The Netherlands under tutelage of Herman Berendsen and his PhD in Chemistry from Penn State under mentorship of Kennie Merz. He worked as a postdoc with Martin Karplus at the Université Louis Pasteur in France and at Harvard University. He started his independent career at Arizona State University and has been on the faculty of the University of South Florida since 2009.