ENTRY INTO MITOSIS IN VERTEBRATE SOMATIC-CELLS IS GUARDED BY A CHROMOSOME-DAMAGE CHECKPOINT THAT REVERSES THE CELL-CYCLE WHEN TRIGGERED DURING EARLY BUT NOT LATE PROPHASE

When vertebrate somatic cells are selectively irradiated in the nucleu s during late prophase (<30 min before nuclear envelope breakdown) the y progress normally through mitosis even if they contain broken chromo somes. However, if early prophase nuclei are similarly irradiated, chr omosome condensation is reversed and the cells return to interphase. T hus, the G(2) checkpoint that prevents entry into mitosis in response to nuclear damage ceases to function in late prophase. If one nucleus in a cell containing two early prophase nuclei is selectively irradiat ed, both return to interphase, and prophase cells that have been induc ed to returned to interphase retain a normal cytoplasmic microtubule c omplex. Thus, damage to an early prophase nucleus is converted into a signal that not only reverses the nuclear events of prophase, but this signal also enters the cytoplasm where it inhibits e.g., centrosome m aturation and the formation of asters. Immunofluorescent analyses reve al that the irradiation-induced reversion of prophase is correlated wi th the dephosphorylation of histone H1, histone H3, and the MPM2 epito pes. Together, these data reveal that a checkpoint control exists in e arly but not late prophase in vertebrate cells that, when triggered, r everses the cell cycle by apparently downregulating existing cyclin-de pendent kinase (CDK1) activity.