VANADATE TRIGGERS THE TRANSITION FROM CHROMOSOME CONDENSATION TO DECONDENSATION IN A MITOTIC MUTANT (TSTM13) - INACTIVATION OF P34(CDC2) H1KINASE AND DEPHOSPHORYLATION OF MITOSIS-SPECIFIC HISTONE H3/

At the nonpermissive temperature (39 degrees C), chromosomes remain co ndensed in a temperature-sensitive cell mutant (tsTM13) arrested in th e late stage of mitosis. Highly increased activity of histone H1 kinas e, hyperphosphorylation of histone H1, and mitosis-specific histone H3 phosphorylation are maintained, even in telophase. In the present stu dy, the defect of chromosome decondensation in tsTM13 cells was found to be partially normalized by a tyrosine phosphatase inhibitor, vanada te, with induction of chromosome decondensation and the formation of m ultinucleated cells. In the presence of vanadate, the H1 kinase activi ty dropped to near normal levels and the amount of the inactive form o f p34(cdc2) protein phosphorylated at a tyrosine residue was increased . H1 and H3 were also extensively de- phosphorylated, the latter being tightly associated with chromosome decondensation. Serine/threonine-p rotein phosphatase in late mitosis of the mutant works normally at 39 degrees C. The results indicate that (a) the genetic defect in the mut ant may be involved in the control mechanism of the p34(cdc2)/H1 kinas e activity in the late M phase rather than the phosphatase, (b) normal ization of the defect of the mutant by vanadate results from inactivat ion of H1 kinase, and (c) late mitosis-specific events (p34(cdc2)/H1 k inase inactivation, mitosis-specific dephosphorylation of histone H1 a nd H3) are closely operating with chromosome decondensation.