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Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation
The WD-repeat proteins Rae1 and Bub3 show extensive sequence homology, indicative of functional similarity. However, previous studies have suggested that Rae1 is involved in the mRNA export pathway and Bub3 in the mitotic checkpoint. To determine the in vivo roles of Rae1 and Bub3 in mammals, we gen...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172680/ https://www.ncbi.nlm.nih.gov/pubmed/12551952 http://dx.doi.org/10.1083/jcb.200211048 |
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author | Babu, J. Ramesh Jeganathan, Karthik B. Baker, Darren J. Wu, Xiaosheng Kang-Decker, Ningling van Deursen, Jan M. |
author_facet | Babu, J. Ramesh Jeganathan, Karthik B. Baker, Darren J. Wu, Xiaosheng Kang-Decker, Ningling van Deursen, Jan M. |
author_sort | Babu, J. Ramesh |
collection | PubMed |
description | The WD-repeat proteins Rae1 and Bub3 show extensive sequence homology, indicative of functional similarity. However, previous studies have suggested that Rae1 is involved in the mRNA export pathway and Bub3 in the mitotic checkpoint. To determine the in vivo roles of Rae1 and Bub3 in mammals, we generated knockout mice that have these genes deleted individually or in combination. Here we show that haplo-insufficiency of either Rae1 or Bub3 results in a similar phenotype involving mitotic checkpoint defects and chromosome missegregation. We also show that overexpression of Rae1 can correct for Rae1 haplo-insufficiency and, surprisingly, Bub3 haplo-insufficiency. Rae1-null and Bub3-null mice are embryonic lethal, although cells from these mice did not have a detectable defect in nuclear export of mRNA. Unlike null mice, compound haplo-insufficient Rae1/Bub3 mice are viable. However, cells from these mice exhibit much greater rates of premature sister chromatid separation and chromosome missegregation than single haplo-insufficient cells. Finally, we show that mice with mitotic checkpoint defects are more susceptible to dimethylbenzanthrene-induced tumorigenesis than wild-type mice. Thus, our data demonstrate a novel function for Rae1 and characterize Rae1 and Bub3 as related proteins with essential, overlapping, and cooperating roles in the mitotic checkpoint. |
format | Text |
id | pubmed-2172680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21726802008-05-01 Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation Babu, J. Ramesh Jeganathan, Karthik B. Baker, Darren J. Wu, Xiaosheng Kang-Decker, Ningling van Deursen, Jan M. J Cell Biol Article The WD-repeat proteins Rae1 and Bub3 show extensive sequence homology, indicative of functional similarity. However, previous studies have suggested that Rae1 is involved in the mRNA export pathway and Bub3 in the mitotic checkpoint. To determine the in vivo roles of Rae1 and Bub3 in mammals, we generated knockout mice that have these genes deleted individually or in combination. Here we show that haplo-insufficiency of either Rae1 or Bub3 results in a similar phenotype involving mitotic checkpoint defects and chromosome missegregation. We also show that overexpression of Rae1 can correct for Rae1 haplo-insufficiency and, surprisingly, Bub3 haplo-insufficiency. Rae1-null and Bub3-null mice are embryonic lethal, although cells from these mice did not have a detectable defect in nuclear export of mRNA. Unlike null mice, compound haplo-insufficient Rae1/Bub3 mice are viable. However, cells from these mice exhibit much greater rates of premature sister chromatid separation and chromosome missegregation than single haplo-insufficient cells. Finally, we show that mice with mitotic checkpoint defects are more susceptible to dimethylbenzanthrene-induced tumorigenesis than wild-type mice. Thus, our data demonstrate a novel function for Rae1 and characterize Rae1 and Bub3 as related proteins with essential, overlapping, and cooperating roles in the mitotic checkpoint. The Rockefeller University Press 2003-02-03 /pmc/articles/PMC2172680/ /pubmed/12551952 http://dx.doi.org/10.1083/jcb.200211048 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Babu, J. Ramesh Jeganathan, Karthik B. Baker, Darren J. Wu, Xiaosheng Kang-Decker, Ningling van Deursen, Jan M. Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation |
title | Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation |
title_full | Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation |
title_fullStr | Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation |
title_full_unstemmed | Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation |
title_short | Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation |
title_sort | rae1 is an essential mitotic checkpoint regulator that cooperates with bub3 to prevent chromosome missegregation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172680/ https://www.ncbi.nlm.nih.gov/pubmed/12551952 http://dx.doi.org/10.1083/jcb.200211048 |
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