CHROMOSOME CONDENSATION INDUCED BY FOSTRIECIN DOES NOT REQUIRE P34(CDC2) KINASE-ACTIVITY AND HISTONE H1 HYPERPHOSPHORYLATION, BUT IS ASSOCIATED WITH ENHANCED HISTONE H2A AND H3 PHOSPHORYLATION

Chromosome condensation at mitosis correlates with the activation of p 34(cdc2) kinase, the hyperphosphorylation of histone H1 and the phosph orylation of histone H3. Chromosome condensation can also be induced b y treating interphase cells with the protein phosphatase 1 and 2A inhi bitors okadaic acid and fostriecin. Mouse mammary tumour FT210 cells g row normally at 32 degrees C, but at 39 degrees C they lose p34(cdc2) kinase activity and arrest in Gz because of a temperature-sensitive le sion in the cdc2 gene. The treatment of these Gz-arrested FT210 cells with fostriecin or okadaic acid resulted in full chromosome condensati on in the absence of p34(cdc2) kinase activity or histone H1 hyperphos phorylation. However, phosphorylation of histones H2A and H3 was stron gly stimulated, partly through inhibition of histone H2A and H3 phosph atases, and cyclins A and B were degraded. The cells were unable to co mplete mitosis and divide, in the presence of the protein kinase inhib itor staurosporine, the addition of fostriecin did not induce histone phosphorylation and chromosome condensation. The results show that chr omosome condensation can take place without either the histone H1 hype rphosphorylation or the p34(cdc2) kinase activity normally associated with mitosis, although it requires a staurosporine-sensitive protein k inase activity. The results further suggest that protein phosphatases 1 and 2A may be important in regulating chromosome condensation by res tricting the level of histone phosphorylation during interphase, there by preventing premature chromosome condensation.