The mitotic spindle and DNA damage-induced apoptosis

EM9 Chinese hamster ovary cells cannot rejoin DNA strand breaks induced by alkylating agents. Ethyl methanesulphonate (EMS)-treated EM9 cells underwen t G2 arrest for a prolonged period followed by entry into mitosis and apopt osis. EM9 cells treated with EMS in G1 entered mitosis 24-36 h after releas e from synchrony, similar to 12 h after untreated control cells, but the mi toses were morphologically abnormal. The spindle-poison nocodazole reduced apoptosis by > 60%, and allowed some cells to complete a second round of DN A replication. We conclude that the assembly of a mitotic spindle, or progr ession beyond the mitotic checkpoint, is important for apoptosis following DNA strand breakage. (C) 2000 Elsevier Science Ireland Ltd. All rights rese rved.