ArticleHuman genetics2008
Gradual reduction of BUBR1 protein levels results in premature sister-chromatid separation then in aneuploidy.
Article in Human genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 94 citations in OpenAlex.
- Functional and clinical evidence for two novel heterozygousFrontiers in endocrinology · 2026Article
- Identification of novel candidate genes associated with meiotic aneuploidy in human embryos by whole-exome sequencing.Journal of assisted reproduction and genetics · 2023Observational
- Spindle assembly checkpoint activation and silencing at kinetochores.Seminars in cell & developmental biology · 2021Review
- Hematopoietic stem cell transplantation in a patient with type 1 mosaic variegated aneuploidy syndrome.Orphanet journal of rare diseases · 2019Article
- BubR1 Insufficiency Impairs Affective Behavior and Memory Function in Mice.International neurourology journal · 2018Article
- The nonmotor adaptor HMMR dampens Eg5-mediated forces to preserve the kinetics and integrity of chromosome segregation.Molecular biology of the cell · 2018Article
- Kinase and Phosphatase Cross-Talk at the Kinetochore.Frontiers in cell and developmental biology · 2018Review
- Association between polymorphisms in segregation genes BUB1B and TTK and gastric cancer risk.Radiology and oncology · 2016Article
- BubR1 is frequently repressed in acute myeloid leukemia and its re-expression sensitizes cells to antimitotic therapy.Haematologica · 2013Article
- Implications of aneuploidy for stem cell biology and brain therapeutics.Frontiers in cellular neuroscience · 2012Article
- Clinical impact of aneuploidy on gastric cancer patients.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2009Review
- TAp73 regulates the spindle assembly checkpoint by modulating BubR1 activity.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biallelic and heterozygous mutations of the BUB1B gene have been reported in mosaic variegated aneuploidy (MVA), a rare disorder characterized by constitutional mosaic aneuploidies associated to severe intrauterine growth retardation, microcephaly and, in most cases, to premature chromatid separation (PCS), highlighting the key role of human BUBR1 in chromosome segregation. To study the consequences of gradual reduction of the BUBR1 protein levels, inhibition of BUB1B expression in model cells was induced using short hairpin RNAs (shRNAs). We obtained stable shRNA-transduced HeLa cells displaying a gradient of residual BUBR1 protein (8.5, 10, 14, 58, and 77%), mimicking the situation of patients' cells harboring one or two BUB1B mutations. Induction of PCS was detected in all transduced cells and its level was correlated to the decrease of BUBR1. Aneuploidy was clearly detected in cells with residual BUBR1 below 50%. Our data demonstrate that the function of the human BUBR1 protein in the spindle checkpoint is remarkably dosage-dependent and that the biological consequences of BUB1B expression reduction on premature chromatid separation and aneuploidy depend on the residual amount of BUBR1. This provides a biological explanation for the mode of inheritance of PCS, which is dominant, and of MVA, which can be recessive in some families and result from the combination of a null allele associated to a common hypomorphic allele in others.
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