INHIBITION OF HISTONE PHOSPHORYLATION BY STAUROSPORINE LEADS TO CHROMOSOME DECONDENSATION

In mammalian cells, hyperphosphorylation of histone H1 and phosphoryla tion of histone H3 correlate well with the G2 phase to metaphase conde nsation of chromosomes, and these phosphorylations most probably have a role in initiating and controlling the entry into mitosis. The prote in kinase inhibitor staurosporine has been used to examine the role of H1 and H3 phosphorylations in controlling chromosome condensation in the mouse FM3A cell line. We present evidence that (i) staurosporine i nhibits the protein kinases that phosphorylate histone H1 during mitos is, (ii) staurosporine also inhibits the histone H3-specific kinase, ( iii) the inhibition of these kinase activities prevent cells from ente ring mitosis, and (iv) addition of staurosporine to cells already arre sted at metaphase by nocodazole causes a rapid dephosphorylation of hi stones H1 and H3 and the decondensation of the metaphase chromosomes. The results show that the hyperphosphorylation of histone H1 and phosp horylation of histone H3 are required to maintain metaphase chromosome s in their condensed state.