Abstract
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.
Highlights
A number of factors are involved in ensuring that in dividing cells chromosomes are copied exactly once and distributed correctly to daughter cells
Metaphase spreads of the hSecurinÀ/À cell line were karyotyped by multiplex fluorescence in situ hybridization (M-FISH) at different passages (Figure 1)
The high rate of chromosome losses in the hSecurinÀ/À cell line had almost vanished by passage 8 (Figure 1C), when chromosome losses were noted in only 10% (2/20) of cells
Summary
A number of factors are involved in ensuring that in dividing cells chromosomes are copied exactly once and distributed correctly to daughter cells. Sister chromatid separation in anaphase depends on the removal of cohesin complexes from chromosomes [2]. In vertebrates removal of cohesin from chromosomes occurs in at least two steps. The ‘‘prophase pathway’’ removes the bulk of cohesin from chromosome arms during prophase and prometaphase [3,4]. At the metaphase-toanaphase transition, residual cohesion is dissolved by the large cysteine endopeptidase separase, which cleaves the socalled kleisin subunit of cohesin (Scc1/Rad in mitosis; Rec in meiosis). This cleavage allows sister chromatids to move apart [7,8] and is, essential for anaphase to occur [9]
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