Molecular basis of chromosome segregation

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Fig.3 Checkpoints

Checkpoint controls (also known as surveillance mechanisms) ensure the dependency of cell-cycle transitions on the completion of earlier events. They consist of three distinct sets of functions: sensors (which look out for defects and emit a signal); signal-transduction cascades (checkpoint signals need to be transmitted throughout the nucleus or cell); and effectors (a target is regulated to delay cell-cycle progression). Checkpoints were first defined genetically by Weinert and Hartwell, with the isolation of rad9 mutants that are defective for the DNA-damage checkpoint. Other checkpoints monitor the completion of DNA replication, spindle-pole position and spindle orientation. In the spindle checkpoint, cells monitor the interaction between chromosomes and microtubules, which takes places at highly specialized regions of chromosomes known as kinetochores4. Unattached kinetochores emit a signal that is transmitted throughout the mitotic machinery to inhibit the onset of anaphase. Other checkpoints act during mitosis. In budding yeast, a Bub2-dependent pathway monitors the position of spindle-pole bodies and only when the mother spindle pole has entered the bud is the completion of anaphase permitted. This pathway clearly regulates the initiation of septation in fission yeast but its conservation and function in vertebrate cells remain to be clearly shown. In fission yeast, a checkpoint that monitors spindle orientation has recently been described. This is activated if the actin cytoskeleton is perturbed during mitosis.