MITOTIC CHROMATIN REGULATES PHOSPHORYLATION OF STATHMIN OP18/

Meiotic and mitotic spindles are required for the even segregation of duplicated chromosomes to the two daughter cells. The mechanism of spi ndle assembly is not fully understood, but two have been proposed that are not mutually exclusive(1-3). The 'search and capture' model sugge sts that dynamic microtubules become progressively captured and stabil ized by the kinetochores on chromosomes, leading to spindle assembly(3 ,4). The 'local stabilization' model proposes that chromosomes change the state of the cytoplasm around them, making it more favourable to m icrotubule polymerization(2,5-9). It has been shown(10,11) that Stathm in/Op18 inhibits microtubule polymerization in vitro by interaction wi th tubulin(12), and that overexpression in tissue culture cells of non -phosphorylatable mutants of Stathmin/Op18 prevents the assembly of mi totic spindles(13). We have used Xenopus egg extracts and magnetic chr omatin beads(14) to show that mitotic chromatin induces phosphorylatio n of Stathmin/Op18. We have also shown the Stathmin/Op18 is one of the factors regulated by mitotic chromatin that governs preferential micr otubule growth around chromosomes during spindle assembly.