Control of DNA replication and cell proliferation in eukaryotes by aphidicolin.
The mycotoxin aphidicolin specifically inhibits nuclear DNA synthesis in eukaryotic cells by intereacting with the replicative DNA polymerase alpha. The drug does not bind directly to DNA nor does it interfere with RNA, protein and nucleic acid precursor synthesis. Aphidicolin offers a new tool for analyzing the mechanism of DNA replication and repair in eukaryotes and for studying the role of eukaryotic DNA polymerases. The drug might also be valuable therapeutically for controlling excessive cell proliferation without adverse effects upon non-multiplying cells. We describe here how to synchronize DNA synthesis in human cells by a double block with aphidicolin and the properties of two human cell lines resistant to the drug.
Spadari
S
S
Istituto di Genetica Biochimica ed Evoluzionistica del CNR, Pavia, Italy.
Pedrali-Noy
G
G
Falaschi
M C
MC
Ciarrocchi
G
G
D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors / Q000235:genetics; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005057:Eukaryotic Cells / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D009154:Mutation; D011817:Rabbits; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D004791:Enzyme Inhibitors; D003208:Concanavalin A; D016590:Aphidicolin; D004256:DNA Polymerase I