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Securin is not required for chromosomal stability in human cells.

Pfleghaar K, Heubes S, Cox J, Stemmann O, Speicher MR - PLoS Biol. (2005)

Bottom Line: Here we show that, after hSecurin knockout through homologous recombination, chromosome losses are only a short, transient effect.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.We propose that human cells possess efficient mechanisms to compensate for the loss of genes involved in chromosome segregation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Human Genetics, Technical University Munich, Munich, Germany.

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.

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Assessment of Chromosomal Stability in Interphase Nuclei of Parental HCT116 Cells and Chromosomally Stable hSecurin−/− Cells Using Centromere-Specific Probes for Chromosomes 7, 8, 11, and 17(A and B) Representative interphase FISH images of parental HCT116 (hSecurin+/+) (A) and hSecurin−/− (B) cell nuclei after hybridization of a four-color probe set consisting of centromere probes for chromosomes 7 (Cy5.5; purple), 8 (FITC; green), 11 (Cy5; blue), and 17 (Cy3; yellow). In each nucleus, two signals are visible for each probe.(C and D) Graphic summary of chromosome gains and losses in parental HCT116 (C) and hSecurin−/− (D) cells. The percentage of signals per nucleus for chromosomes 7, 8, 11, and 17 was determined from 300 cells of each genotype (100 cells each in three separate experiments).
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pbio-0030416-g002: Assessment of Chromosomal Stability in Interphase Nuclei of Parental HCT116 Cells and Chromosomally Stable hSecurin−/− Cells Using Centromere-Specific Probes for Chromosomes 7, 8, 11, and 17(A and B) Representative interphase FISH images of parental HCT116 (hSecurin+/+) (A) and hSecurin−/− (B) cell nuclei after hybridization of a four-color probe set consisting of centromere probes for chromosomes 7 (Cy5.5; purple), 8 (FITC; green), 11 (Cy5; blue), and 17 (Cy3; yellow). In each nucleus, two signals are visible for each probe.(C and D) Graphic summary of chromosome gains and losses in parental HCT116 (C) and hSecurin−/− (D) cells. The percentage of signals per nucleus for chromosomes 7, 8, 11, and 17 was determined from 300 cells of each genotype (100 cells each in three separate experiments).

Mentions: Interphase FISH confirmed that hSecurin−/− cells at passage 12 were indeed chromosomally stable, similarly to the parental cell line HCT116 (Figure 2).


Securin is not required for chromosomal stability in human cells.

Pfleghaar K, Heubes S, Cox J, Stemmann O, Speicher MR - PLoS Biol. (2005)

Assessment of Chromosomal Stability in Interphase Nuclei of Parental HCT116 Cells and Chromosomally Stable hSecurin−/− Cells Using Centromere-Specific Probes for Chromosomes 7, 8, 11, and 17(A and B) Representative interphase FISH images of parental HCT116 (hSecurin+/+) (A) and hSecurin−/− (B) cell nuclei after hybridization of a four-color probe set consisting of centromere probes for chromosomes 7 (Cy5.5; purple), 8 (FITC; green), 11 (Cy5; blue), and 17 (Cy3; yellow). In each nucleus, two signals are visible for each probe.(C and D) Graphic summary of chromosome gains and losses in parental HCT116 (C) and hSecurin−/− (D) cells. The percentage of signals per nucleus for chromosomes 7, 8, 11, and 17 was determined from 300 cells of each genotype (100 cells each in three separate experiments).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1287505&req=5

pbio-0030416-g002: Assessment of Chromosomal Stability in Interphase Nuclei of Parental HCT116 Cells and Chromosomally Stable hSecurin−/− Cells Using Centromere-Specific Probes for Chromosomes 7, 8, 11, and 17(A and B) Representative interphase FISH images of parental HCT116 (hSecurin+/+) (A) and hSecurin−/− (B) cell nuclei after hybridization of a four-color probe set consisting of centromere probes for chromosomes 7 (Cy5.5; purple), 8 (FITC; green), 11 (Cy5; blue), and 17 (Cy3; yellow). In each nucleus, two signals are visible for each probe.(C and D) Graphic summary of chromosome gains and losses in parental HCT116 (C) and hSecurin−/− (D) cells. The percentage of signals per nucleus for chromosomes 7, 8, 11, and 17 was determined from 300 cells of each genotype (100 cells each in three separate experiments).
Mentions: Interphase FISH confirmed that hSecurin−/− cells at passage 12 were indeed chromosomally stable, similarly to the parental cell line HCT116 (Figure 2).

Bottom Line: Here we show that, after hSecurin knockout through homologous recombination, chromosome losses are only a short, transient effect.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.We propose that human cells possess efficient mechanisms to compensate for the loss of genes involved in chromosome segregation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Human Genetics, Technical University Munich, Munich, Germany.

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.

Show MeSH
Related in: MedlinePlus