ZW10 HELPS RECRUIT DYNACTIN AND DYNEIN TO THE KINETOCHORE

Mutations in the Drosophila melanogaster zw10 gene, which encodes a co nserved, essential kinetochore component, abolish the ability of dynei n to localize to kinetochores. Several similarities between the behavi or of ZW10 protein and dynein further support a role for ZW10 in the r ecruitment of dynein to the kinetochore: (a) in response to bipolar te nsion across the chromosomes, both proteins mostly leave the kinetocho re at metaphase, when their association with the spindle becomes appar ent; (b) ZW10 and dynein both bind to functional neocentromeres of str ucturally acentric minichromosomes; and (c) the localization of both Z W10 and dynein to the kinetochore is abolished in cells mutant for the gene rough deal. ZW10's role in the recruitment of dynein to the kine tochore is likely to be reasonably direct, because dynamitin, the p50 subunit of the dynactin complex, interacts with ZW10 in a yeast two-hy brid screen. Since in zw10 mutants no defects in chromosome behavior a re observed before anaphase onset, our results suggest that dynein at the kinetochore is essential for neither microtubule capture nor congr ession to the metaphase plate. Instead, dynein's role at the kinetocho re is more likely to be involved in the coordination of chromosome sep aration and/or poleward movement at anaphase onset.