The role of the pericentromere in mitosis and meiosis.

The region surrounding the centromere, the pericentromere, plays a central role in coordinating the linkages between chromosomes that are essential for accurate chromosome segregation. Here I propose to uncover the regulatory mechanisms that operate at the pericentromere to achieve these functions during both mitosis and meiosis. I will use both budding yeast, which has simple pericentromeres, together with fission yeast, the pericentromeres of which more closely resemble those of humans, to dis sect the defining features of the pericentromere. A conserved property of the pericentromere is its ability to attract high levels of cohesin, the protein complex that holds newly duplicated chromosomes together until their separation upon chromosome segregation. We will use directed approaches to reveal how factors in the kinetochore specify the pericentromere for cohesin enrichment. We will also determine the role of the pericentromere in regulating the release of this cohesin through an alte rnative pathway for controlling anaphase onset which we recently discovered. Finally, we will identify the changes that occur at the pericentromere during meiosis by elucidating the meiosis-specific roles of general regulatory factors and though genomic and proteomic screens. Together, these goals will lead us to a detailed molecular picture of the pericentromere during mitosis and meiosis.