Regulated separation of sister chromatids is the key event of mitosis. Sister chromatids remain cohered from the moment of DNA duplication until anaphase. Two known factors account for cohesion: DNA catenations and cohesin complexes. Premature loss of centromeric cohesion is prevented by the spindle checkpoint. Here we show that sororin, a protein implicated in promoting cohesion through effects on cohesin complexes, is involved in maintenance of cohesion in response to the spindle checkpoint. Sororin-depleted cells reach prometaphase with cohered sister chromatids and are able to form metaphase plates. However, loss of cohesion in anaphase is asynchronous and cells are unresponsive to the spindle checkpoint, accumulating with separated sisters scattered throughout the cytoplasm. These phenotypes are similar to those seen after Shugoshin depletion, suggesting that sororin and Shugoshin might act in concert. Furthermore, sororin-depleted and Shugoshin-depleted cells lose cohesion indepen-dently of the APC/C. Therefore, sororin and Shugoshin protect centromeric cohesion in response to the spindle checkpoint, but prevent the removal of cohesion by a mechanism independent of the APC/C.
Bibliographical noteFunding Information:
We thank S. Rankin, M. Kirschner, A. Salic and T. Mitchison for reagents. R. Johnson, K. Evenson and L. Lanier for use of facilities. This work was funded by NIH grant CA099033 (DJC). J.F.G.A. was funded in part by MEC-Spain (DGI) grant BFU2004-03418/BMC and L.A.D.M. in part by CONACyT (#167426).
- Chromosome cohesion
- Spindle checkpoint