Insights into Shugoshin localization and function in S. cerevisiae chromosome segregation

Abstract

Faithful chromosome segregation is crucial to the well being of organisms. In mitosis, the partitioning of chromosomes to daughter cells is monitored at many levels to ensure that identical genomic information is received. Meiosis is a specialized form of cell division during which two division phases follow replication of the genome. Several steps are taken in meiosis to allow for a unique pattern of chromosome segregation. Homologous chromosomes segregate during the first division and sister chromatids segregate during the second. Cohesins, protein complexes that associate along the length of chromosomes during DNA replication, are lost in a step-wise manner in meiosis. During the first division, cohesins are lost only along chromosome arms. Cohesins remain at centromeres during meiosis II and are required to establish proper orientation of sister chromatid kinetochores. Shugoshin (Sgo1) is a protein related to D. melanogaster Mei-S332 that is crucial for the protection of centromeric cohesins from cleavage until anaphase II of meiosis. Here we show that in S. cerevisiae cohesins are protected from cleavage during meiosis I in a 50 kb region of chromosomes and Sgo1 localizes to cohesin-associated regions within this region. Interestingly, there is no sequence specificity to the region of Sgo1 association. Instead, it is the proximity of this region to the centromere that causes enhanced cohesin and Sgol localization. We also characterize a role for Sgo1 in chromosome segregation that is independent of its role in cohesin regulation. Sgo1 helps ensure that kinetochores are oriented correctly in both mitosis and meiosis and is required to prevent chromosome segregation errors and spindle elongation in the absence of cohesin cleavage.

(cont.,) Finally, our data suggest a possible role for Sgo1 in biasing sister kinetochores toward bi-orientation during the mitotic divisions. Thus, Sgol is a centromeric protein with a cell cycle role that includes both regulations of cohesins and kinetochore orientation.