The Nogales Lab

Wednesday, May 14, 2008

In the cell the dynamics of microtubules is regulated by their interaction with different factors. Of special interest is the coupling of microtubules to the kinetochore, a process where microtubule dynamics reaches its "climax".

In collaboration with Georjana Barnes and David Drubin we are studying how the yeast kinetochore complex Dam1 binds and tracks microtubule plus ends. The complex self-assembles into rings and helices dam1 around the microtubule wall (Westermann et al., Mol Cell 2005). The binding is enhanced for GMPCPP microtubules, supporting a preferential binding to growing microtubule ends. The interaction is via the charged C-terminal of tubulin and allows for ring sliding along microtubules, which can be coupled to microtubule disassembly to allow for the movement of Dam1 as it remains attached to a depolymerizing end (Westermann et al., Nature 2006). This explains how this ring structure is able to track the depolymerizing ends of microtubules (as during anaphase), without requiring energy!

After these mechanistic studies we look forward to concentrating on the structure of the Dam1 ring. Furthermore, a number of kinetochore proteins bind to Dam1 and link it to the chromosome, and we plan to characterize these interactions toward a structural understanding of the molecular mechanisms underlying faithful chromosome segregation.