Regulation of Centromeric Cohesion by Sororin Independently of the APC/C

Abstract

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 independently 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.

Regulation of sororin by Cdk1-mediated phosphorylation

“…Cells blocked in mitosis as a result of sororin knockdown were characterized by misaligned chromosomes that did not form a metaphase plate (Fig. 8B), similar to previous reports (Diaz-Martinez et al, 2007;Schmitz et al, 2007). Reconstituting with either sororin WT-V5 or 9A-V5 reduced the percentage of cells in mitosis (Fig.…”

Cohesins and Cohesin-Regulators in Meiosis

“…Sororin is ubiquitinized and degraded after sister chromatid cohesion is dissolved (Rankin, 2005). Studies on Sororin-depleted and Shugoshin-depleted cells indicate that both proteins might act in concert in the protection of centromeric cohesion (Diaz-Martinez, et al, 2007). Sororin is also needed for maintaining stable chromatin-bound cohesin and DSBs repair in G2 (Schmitz et al, 2007).…”

“…Regarding to the Sororin, it has been described in culture cells that this protein have a role in centromere cohesion, probably it is implicated in the protection of centromeric cohesin complexes (Diaz-Martinez et al, 2007). Moreover Sororin seems to have a role in the cohesion establishment during replication (Lafont et al, 2010).…”

C-terminus of Sororin interacts with SA2 and regulates sister chromatid cohesion

“…These results are consistent with the previous observations. 18 Unlike the control cells, in which the segregated chromosomes formed 2 compact round or oval-shaped nuclei that were pulled apart toward the opposite poles, the separated chromosomes in the Sororin-silenced cells were loose and dispersed, and they were not pulled apart to the opposite poles ( Figure S1B). The overall chromosomal mass in the resulting daughter cells also appeared unequal in the Sororin knockdown cells but not in the control cells ( Figure S1B), indicating a critical chromatid separation defect.…”