Defining the molecular mechanism targeting CENP-E to centrosomes (360G-Wellcome-207153_Z_17_Z)

Accurate distribution of the genetic material to the daughter cells is essential to ensure correct progression through cell division. There is an ATP-dependent mechanism in place to ensure the alignment of all chromosomes. CENP-E is a motor protein that mediates chromosome capture and bi-orientation during mitosis. CENP-E is also found at centrosomes, where it is thought to be loaded, to then walk to microtubule ends bound to kinetochores. Its function at centrosomes is unclear. However in yeast, it has been suggested that kinesins bring the spindle checkpoint proteins to kinetochores from centrosomes. CENP-E may therefore in human cells bring the checkpoint proteins to unattached kinetochores. Here, we will crystallize the centrosome-targeting domain of CENP-E and define its sequence requirements using site-directed mutagenesis of conserved residues to test its recruitment to centrosome to gain insights into the role of motor proteins at centrosomes.