Novel response to microtubule perturbation in meiosis.

During the mitotic cell cycle, microtubule depolymerization leads to a cell cycle arrest in metaphase, due to activation of the spindle checkpoint. Here, we show that under microtubule-destabilizing conditions, such as low temperature or the presence of the spindle-depolymerizing drug benomyl, meiotic budding yeast cells arrest in G(1) or G(2), instead of metaphase. Cells arrest in G(1) if microtubule perturbation occurs as they enter the meiotic cell cycle and in G(2) if cells are already undergoing premeiotic S phase.

Amplitude control of cell-cycle waves by nuclear import.

Propagation of waves of biochemical activities through consecutive stages of the cell cycle is essential to execute the steps of cell division in a strict temporal order. Mechanisms that ensure the proper amplitude and timing of these waves are poorly understood. Using a synthetic gene circuit, we show that a transcriptional activator driven by yeast cell-cycle promoters propagates transcriptional oscillations with substantial damping.

Mitotic exit regulation through distinct domains within the protein kinase Cdc15.

The mitotic exit network (MEN), a Ras-like signaling cascade, promotes the release of the protein phosphatase Cdc14 from the nucleolus and is essential for cells to exit from mitosis in Saccharomyces cerevisiae. We have characterized the functional domains of one of the MEN components, the protein kinase Cdc15, and investigated the role of these domains in mitotic exit. We show that a region adjacent to Cdc15's kinase domain is required for self-association and for binding to spindle pole bodies and that this domain is essential for CDC15 function.

DNA stability and schizophrenia in twins.

The goal of these experiments was to understand DNA changes relevant to schizophrenia. This work compared DNA of monozygotic (MZ) twins surrounding (CAG)(n) repeating sequences, and characterized the relationship between fragile sites and schizophrenia. Twelve twin-pairs, previously classified as MZ and 18 unrelated sib-pairs, from seven families were studied.