POLYAMINES MAY REGULATE S-PHASE PROGRESSION BUT NOT THE DYNAMIC CHANGES OF CHROMATIN DURING THE CELL-CYCLE

Several studies suggest that polyamines may stabilize chromatin and pl ay a role in its structural alterations. In line with this idea, we fo und here by chromatin precipitation and micrococcal nuclease (MNase) d igestion analyses, that spermidine and spermine stabilize or condense the nucleosomal organization of chromatin in vitro. We then investigat ed the possible physiological role of polyamines in the nucleosomal or ganization of chromatin during the cell cycle in Chinese hamster ovary (CHO) cells deficient in ornithine decarboxylase (ODC) activity. An e xtended polyamine deprivation (for 4 days) was found to arrest 70% of the odc(-) cells in S phase. MNase digestion analyses revealed that th ese cells have a highly loosened and destabilized nucleosomal organiza tion. However, no marked difference in the chromatin structure was det ected between the control and polyamine-depleted cells following the s ynchronization of the cells at the S-phase. We also show in synchroniz ed cells that polyamine deprivation retards the traverse of the cells through the S phase already in the first cell cycle. Depletion of poly amines had no significant effect on the nucleosomal organization of ch romatin in G(1)-early S. The polyamine-deprived cells were also capabl e of condensing the nucleosomal organization of chromatin in the S/G(2 ) phase of the cell cycle. These data indicate that polyamines do not regulate the chromatin condensation state during the cell cycle, altho ugh they might have some stabilizing effect on the chromatin structure . Polyamines may, however, play an important role in the control of S- phase progression. (C) 1998 Wiley-Liss, Inc.