Abnormalities of chromosome number are frequently observed in cancers. The mechanisms regulating chromosome segregation in human cells are therefore of great interest. Recently it has been reported that human cells without an hSecurin gene lose chromosomes at a high frequency. Here we show that, after hSecurin knockout through homologous recombination, chromosome losses are only a short, transient effect. After a few passages hSecurin−/− cells became chromosomally stable and executed mitoses normally. This was unexpected, as the securin loss resulted in a persisting reduction of the sister-separating protease separase and inefficient cleavage of the cohesin subunit Scc1. Our data demonstrate that securin is dispensable for chromosomal stability in human cells. We propose that human cells possess efficient mechanisms to compensate for the loss of genes involved in chromosome segregation.

The highly abundant AAA-ATPase p97 is required for diverse cellular processes, of which ER-associated protein degradation (ERAD) is understood best. Previously, a new role of p97 in spindle disassembly at the end of mitosis has been reported. However, we show that neither addition of dominant-negative p97 mutants nor depletion of crucial p97 adaptors impairs transition of meiotic spindles into interphase arrays of microtubules. The dominant-negative approach is validated by inhibition of ERAD, which we reconstitute for the first time in the powerful biochemical system of Xenopus egg extracts. The role of p97 in spindle disassembly during meiotic exit should therefore be reconsidered.

Mature Xenopus oocytes are arrested in meiosis by the activity of XErp1/Emi2, an inhibitor of the ubiquitin-ligase anaphasepromoting complex/cyclosome (APC/C). On fertilization, XErp1 is degraded, resulting in APC/C activation and the consequent degradation of cell-cycle regulators and exit from meiosis. In this study, we show that a modest increase in the activity of the ubiquitin-conjugating enzyme UbcX overrides the meiotic arrest in an APC/C-dependent reaction. Intriguingly, XErp1 remains stable in these conditions. We found that UbcX causes the ubiquitylation of XErp1, followed by its dissociation from the APC/C. Our data support the idea that ubiquitylation regulates the APC/C-inhibitory activity of XErp1.

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