Establishment of dependence relationships between genome replication and mitosis.
Although budding yeast cell biology and genetics provided a powerful system to isolate S-phase checkpoint mutants, initial studies relied on a defect not likely to be relevant in higher eukaryotes. The first mutants were isolated for their inability to restrain mitotic spindle elongation in S-phase. Since most eukaryotes do not assemble spindles until prometaphase the validity of this approach might have been questioned. However, these early studies were designed with a highly valid assumption in mind; that checkpoints have a variety of targets, but comprise conserved kinase cascades that make up these signaling pathways. The task that lies ahead is to determine targets of the S-phase checkpoint relevant to mammals. One step forward might be the realization that the budding yeast S-phase checkpoint prevents loss of sister chromatid cohesion while DNA replication is ongoing. If this mechanism is conserved in mammals, it could prove vital for chromosome segregation fidelity.
Clarke
Duncan J
DJ
Department of Genetics, Cell Biology, and Development, University of Minnesota Medical School, 420 Washington Avenue SE, Minneapolis, Minnesota 55455, USA. Duncan.J.Clarke-2@umn.edu
D000818:Animals; D002842:Chromatids / Q000378:metabolism / Q000648:ultrastructure*; D004247:DNA / Q000096:biosynthesis*; D005800:Genes, Fungal; D016678:Genome; D006801:Humans; D008938:Mitosis; D008954:Models, Biological; D016196:S Phase; D015398:Signal Transduction; D008941:Spindle Apparatus
D004247:DNA