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 EM9cells underwent G2 arrest for a prolonged period followed by entry into mitosis and apoptosis. EM9 cells treated with EMS in G1 entered mitosis 24-36 h after release from synchrony, approximately 12 h after untreated control cells, but the mitoses were morphologically abnormal. The spindle-poison nocodazole reduced apoptosis by greater than 60%, and allowed some cells to complete a second round of DNA replication. We conclude that the assembly of a mitotic spindle, or progression beyond the mitotic checkpoint, is important for apoptosis following DNA strand breakage.
Johnson
P A
PA
School of Biological Sciences, G.38 Stopford Building, University of Manchester, Oxford Road, Manchester, UK.
Clements
P
P
Hudson
K
K
Caldecott
K W
KW
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000187:drug effects*; D005020:Ethyl Methanesulfonate / Q000633:toxicity*; D005434:Flow Cytometry; D008941:Spindle Apparatus / Q000187:drug effects*
D018906:Antineoplastic Agents, Alkylating; D004277:DNA, Single-Stranded; D005020:Ethyl Methanesulfonate