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. (C) 2002 Wiley-Liss, Inc.