title: The plant amino acid mimosine may inhibit initiation at origins of replication in Chinese hamster cells.
abstract: An understanding of replication initiation in mammalian cells has been hampered by the lack of mutations and/or inhibitors that arrest cells just prior to entry into the S period. The plant amino acid mimosine has recently been suggested to inhibit cells at a regulatory step in late G1. We have examined the effects of mimosine on cell cycle traverse in the mimosine [corrected]-resistant CHO cell line CHOC 400. When administered to cultures for 14 h after reversal of a G0 block, the drug appears to arrest the population at the G1/S boundary, and upon its removal cells enter the S phase in a synchronous wave. However, when methotrexate is administered to an actively dividing asynchronous culture, cells are arrested not only at the G1/S interface but also in early and middle S phase. Most interestingly, two-dimensional gel analysis of replication intermediates in the initiation locus of the amplified dihydrofolate reductase domain suggests that mimosine may actually inhibit initiation. Thus, this drug represents a new class of inhibitors that may open a window on regulatory events occurring at individual origins of replication.
authors.affiliation: Biochemistry Department, University of Virginia School of Medicine, Charlottesville 22908.
authors.forename: P J
authors.initials: PJ
authors.lastname: Mosca
authors.forename: P A
authors.initials: PA
authors.lastname: Dijkwel
authors.forename: J L
authors.initials: JL
authors.lastname: Hamlin
mesh_terms: D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D004261:DNA Replication / Q000187:drug effects*; D015180:Electrophoresis, Gel, Two-Dimensional; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D007700:Kinetics; D008898:Mimosine / Q000494:pharmacology*; D010944:Plants; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D013936:Thymidine / Q000037:antagonists & inhibitors
chemical_list: D016590:Aphidicolin; D008898:Mimosine; D013762:Tetrahydrofolate Dehydrogenase; D013936:Thymidine