To prevent inaccurate chromosome segregation from occurring during mitosis, duplicated sister chromatids are held together by so-called cohesin proteins until the cell is ready to divide into daughter cells. Two mechanisms regulate chromatid segregation — first, cohesins dissociate from the chromosomal arms during prophase, and then the remaining cohesins at the centromere are cleaved at the onset of anaphase. Now, Jasmin Dynek and Susan Smith report that there is a third mechanism — telomere-specific cohesion — with an essential role in chromatid separation.

When the authors inhibited tankyrase-1 expression in cultured cells, the cells arrested and a threefold increase in the G2–M cell population was detected by fluorescence-activated-cell-sorting analysis. The arrested cells, which contained abnormal mitotic chromosomes of three distinct phenotypes, were rescued by re-expression of tankyrase-1. This indicated that tankyrase-1 is important for cell-cycle progression. Close examination of the abnormal chromosomes revealed separated centromeres, which indicated that cells were arrested in anaphase. So what causes this cell-cycle arrest?

The progression from metaphase to anaphase is regulated by the anaphase-promoting complex, which functions normally in the tankyrase-1-deficient cells. As tankyrase-1 regulates telomere length, the authors wondered whether abnormal telomeres were responsible for the cell-cycle arrest. Telomeres were capped normally and there was no evidence of DNA damage or telomeric-fusion products in the tankyrase-1-deficient cells. So, cell-cycle arrest was not the result of defective telomeres.

Next, the authors analysed the telomeres using fluorescence in situ hybridization. The telomeric regions in cells that lacked tankyrase-1 expression appeared as two singlets, whereas in control cells telomeric regions generally appeared as doublets. Double staining of chromosomal arms and telomeres in the same cell showed that the chromosome arms were separated in tankyrase-1-deficient cells (they appeared as doublets), whereas telomeres appeared as singlets. So, although chromosomes replicated normally in these cells, only the arms — but not the telomeres — separated.

Presumably, replicated telomeres are held together by telomere-specific cohesion complexes, which are somehow released by tankyrase-1. Whether these cohesion complexes contain cohesin remains to be established. This new regulatory mechanism for sister-chromatid separation could represent a checkpoint, which ensures that intact chromosomes are passed on to daughter cells.