Cell Biology

Separation Anxiety

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Science  22 Jun 2001:
Vol. 292, Issue 5525, pp. 2221
DOI: 10.1126/science.292.5525.2221a

In a dividing cell, sister chromatids containing the newly replicated DNA remain tightly associated until the onset of anaphase, at which point they begin to move to opposite poles of the cell. Disruptions in chromatid segregation result in loss or gain of chromosomes in the daughter cells, a situation commonly seen in cancer cells. One of the molecules regulating chromosome segregation is securin (called Pds1p in budding yeast), a protein that paradoxically appears to both inhibit and promote chromatid segregation by altering the functional state of separin, a protease. Separin is required for chromatid separation because it cleaves cohesin, the protein that holds the sister chromatids together.

In work that illustrates how easily cancer cells can acquire a chromosomal instability phenotype, Jallepalli et al. show that deletion of the securin gene is in itself sufficient to convert a chromosomally stable human cancer cell into an unstable one that suffers frequent chromosome loss during division. The chromosome loss in the securin-deficient cells is due to impaired chromatid segregation and is associated with defective activation of separin. The viability and continued proliferation of these cells is somewhat surprising, but might be explained by the results of Alexandru et al., who document the existence of a second surveillance system for chromatid segregation that is operative in the absence of securin. In a study of budding yeast, they find that sister chromatid separation is regulated by phosphorylation of serine residues in cohesin near the site cleaved by separin. These phosphorylation events enhance cohesin cleavage and are mediated by Polo/Cdc5 kinase, which has been implicated previously in many aspects of cell cycle control. Finally, in a study of yeast, Clarke et al. link Pds1/securin to two distinct cell cycle checkpoints: the G2 DNA-damage checkpoint and a late S-phase checkpoint. The latter likely ensures that chromatids do not separate until DNA replication is complete. — PAK

Cell105, 445; 459 (2001); Nature Cell Biol. 3, 619 (2001).

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