Whether yeast can undergo apoptosis is controversial – as is the idea that this involves the metacaspase Yca1p, since Yca1p is only a distant relative of the caspases that drive apoptosis in metazoans. In higher organisms, apoptosis is often linked to inactivation of proteins involved in initiation of DNA replication and cell cycle checkpoints. William Burhans and co-workers have therefore examined whether the same is true of budding yeast (see ). They observe that temperature-sensitive orc2-1 mutations, which simultaneously inhibit assembly of the DNA pre-replication complex (pre-RC) and DNA checkpoints, cause yeast cells to undergo apoptosis when shifted to the restrictive temperature. This is accompanied by activation of Yca1p and generation of reactive oxygen species (ROS). Moreover, the authors show that deleting the YCA1 gene partially suppresses the effect. They therefore argue that Yca1p activation contributes to yeast apoptosis. They propose that this occurs in response to DNA damage associated with defective checkpoints and insufficient numbers of replication forks. The possibility that yeast can be used as a model system to investigate links between DNA damage and apoptosis is exciting, because these are often disrupted in cancer.
