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Loss of ATRX leads to chromosome cohesion and congression defects
αThalassemia/mental retardation X linked (ATRX) is a switch/sucrose nonfermenting-type ATPase localized at pericentromeric heterochromatin in mouse and human cells. Human ATRX mutations give rise to mental retardation syndromes characterized by developmental delay, facial dysmorphisms, cognitive def...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213576/ https://www.ncbi.nlm.nih.gov/pubmed/18227278 http://dx.doi.org/10.1083/jcb.200706083 |
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author | Ritchie, Kieran Seah, Claudia Moulin, Jana Isaac, Christian Dick, Frederick Bérubé, Nathalie G. |
author_facet | Ritchie, Kieran Seah, Claudia Moulin, Jana Isaac, Christian Dick, Frederick Bérubé, Nathalie G. |
author_sort | Ritchie, Kieran |
collection | PubMed |
description | αThalassemia/mental retardation X linked (ATRX) is a switch/sucrose nonfermenting-type ATPase localized at pericentromeric heterochromatin in mouse and human cells. Human ATRX mutations give rise to mental retardation syndromes characterized by developmental delay, facial dysmorphisms, cognitive deficits, and microcephaly and the loss of ATRX in the mouse brain leads to reduced cortical size. We find that ATRX is required for normal mitotic progression in human cultured cells and in neuroprogenitors. Using live cell imaging, we show that the transition from prometaphase to metaphase is prolonged in ATRX-depleted cells and is accompanied by defective sister chromatid cohesion and congression at the metaphase plate. We also demonstrate that loss of ATRX in the embryonic mouse brain induces mitotic defects in neuroprogenitors in vivo with evidence of abnormal chromosome congression and segregation. These findings reveal that ATRX contributes to chromosome dynamics during mitosis and provide a possible cellular explanation for reduced cortical size and abnormal brain development associated with ATRX deficiency. |
format | Text |
id | pubmed-2213576 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22135762008-07-28 Loss of ATRX leads to chromosome cohesion and congression defects Ritchie, Kieran Seah, Claudia Moulin, Jana Isaac, Christian Dick, Frederick Bérubé, Nathalie G. J Cell Biol Research Articles αThalassemia/mental retardation X linked (ATRX) is a switch/sucrose nonfermenting-type ATPase localized at pericentromeric heterochromatin in mouse and human cells. Human ATRX mutations give rise to mental retardation syndromes characterized by developmental delay, facial dysmorphisms, cognitive deficits, and microcephaly and the loss of ATRX in the mouse brain leads to reduced cortical size. We find that ATRX is required for normal mitotic progression in human cultured cells and in neuroprogenitors. Using live cell imaging, we show that the transition from prometaphase to metaphase is prolonged in ATRX-depleted cells and is accompanied by defective sister chromatid cohesion and congression at the metaphase plate. We also demonstrate that loss of ATRX in the embryonic mouse brain induces mitotic defects in neuroprogenitors in vivo with evidence of abnormal chromosome congression and segregation. These findings reveal that ATRX contributes to chromosome dynamics during mitosis and provide a possible cellular explanation for reduced cortical size and abnormal brain development associated with ATRX deficiency. The Rockefeller University Press 2008-01-28 /pmc/articles/PMC2213576/ /pubmed/18227278 http://dx.doi.org/10.1083/jcb.200706083 Text en Copyright © 2008, 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 | Research Articles Ritchie, Kieran Seah, Claudia Moulin, Jana Isaac, Christian Dick, Frederick Bérubé, Nathalie G. Loss of ATRX leads to chromosome cohesion and congression defects |
title | Loss of ATRX leads to chromosome cohesion and congression defects |
title_full | Loss of ATRX leads to chromosome cohesion and congression defects |
title_fullStr | Loss of ATRX leads to chromosome cohesion and congression defects |
title_full_unstemmed | Loss of ATRX leads to chromosome cohesion and congression defects |
title_short | Loss of ATRX leads to chromosome cohesion and congression defects |
title_sort | loss of atrx leads to chromosome cohesion and congression defects |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213576/ https://www.ncbi.nlm.nih.gov/pubmed/18227278 http://dx.doi.org/10.1083/jcb.200706083 |
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