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Aneuploidy directly results from the mis-segregation of sister chromatids during mitosis. Cohesion of sister chromatids in eukaryotes is primarily achieved by the cohesin complex. Sgo1, an evolutionarily conserved protein, functions to protect centromeric cohesin as depletion of Sgo1 results in precocious chromosomal segregation and massive mitotic arrest. Consistent with several early studies, we demonstrate that human Sgo1 is kinetochore-localized and required for accurate segregation of mitotic chromosomes. Recently, we reveal the existence of a major isoform of Sgo1 that exhibits an entirely different subcellular localization pattern. The full-length Sgo1 primarily localizes to kinetochores during G2 phase and mitotic prophase, metaphase, and anaphase. On the other hand, the short isoform of Sgo1 (sSgo1) that lacks exon 6 does not localize to kinetochores during any stages of the cell cycle; instead, it is enriched at spindle poles and mitotic spindles. Mitotic Sgo1 exhibits a retarded mobility on denatured gels; protein phosphatase treatment converts it into the interphase form, indicating that Sgo1 is subjected to the regulation by phosphorylation. Moreover, treatment of HeLa cells with MG132 greatly stabilizes both Sgo1 and sSgo1, suggesting that the ubiquitination and proteasome pathway is involved in regulating their stability during the cell cycle. Together, our studies suggest that Sgo1 is an important mitotic component whose function is tightly controlled by a variety of cellular and molecular mechanisms.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA