Proper chromosome segregation largely relies on the persistence of sister chromatid cohesion until anaphase as well as the correct attachment of microtubules to kinetochores. Premature separation of sister chromatids can lead to chromosome instability and give rise to cancer. Shugoshin (SGO), an evolutionarily conserved protein, is involved in protecting sister chromatid cohesion during mitosis and meiosis. Mammalian cells contain two major isoforms of SGO1: a longer SGO1A and a shorter SGO1C. Current understanding on the role of SGO1 is largely based on functional disruption of all SGO1 in the cell. Hence little is known about the differential role of the various SGO1 isoforms. I found that among the two isoforms, SGO1A is sufficient for regulating proper mitotic progression. C...[ Read more ]

Proper chromosome segregation largely relies on the persistence of sister chromatid cohesion until anaphase as well as the correct attachment of microtubules to kinetochores. Premature separation of sister chromatids can lead to chromosome instability and give rise to cancer. Shugoshin (SGO), an evolutionarily conserved protein, is involved in protecting sister chromatid cohesion during mitosis and meiosis. Mammalian cells contain two major isoforms of SGO1: a longer SGO1A and a shorter SGO1C. Current understanding on the role of SGO1 is largely based on functional disruption of all SGO1 in the cell. Hence little is known about the differential role of the various SGO1 isoforms. I found that among the two isoforms, SGO1A is sufficient for regulating proper mitotic progression. Cells with ectopic expression of SGO1C behave similarly to cells depleted of SGO1 in terms of the activation of the spindle-assembly checkpoint, sister chromatid cohesion, and the maintenance of centrosomes. Ectopic expression of SGO1C arrests cells in mitosis in a spindle-assembly checkpoint-dependent manner. Moreover, the cells contain separated sister chromatids and an extra centrosome foci. From these data, I propose that SGO1C is likely to act in a dominant negative manner to inhibit the functions of SGO1A. Notably, SGO1C’s effect on SGO1A function is independent of its kinetochore localization and the restoration of SGO1C phenotype involves a re-localization of SGO1A. However, due to the differential affinity to form homodimer and heterodimer, re-localization of SGO1A is unlikely through a direct interaction with SGO1C. Collectively, these data indicate that although SGO1C does not play a major role in mitosis, overexpression of SGO1C severely impairs normal mitotic progression.