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Mi-2/NuRD complex function is required for normal S phase progression and assembly of pericentric heterochromatin
During chromosome duplication, it is essential to replicate not only the DNA sequence, but also the complex nucleoprotein structures of chromatin. Pericentric heterochromatin is critical for silencing repetitive elements and plays an essential structural role during mitosis. However, relatively litt...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164457/ https://www.ncbi.nlm.nih.gov/pubmed/21737684 http://dx.doi.org/10.1091/mbc.E11-03-0258 |
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author | Sims, Jennifer K. Wade, Paul A. |
author_facet | Sims, Jennifer K. Wade, Paul A. |
author_sort | Sims, Jennifer K. |
collection | PubMed |
description | During chromosome duplication, it is essential to replicate not only the DNA sequence, but also the complex nucleoprotein structures of chromatin. Pericentric heterochromatin is critical for silencing repetitive elements and plays an essential structural role during mitosis. However, relatively little is understood about its assembly and maintenance during replication. The Mi2/NuRD chromatin remodeling complex tightly associates with actively replicating pericentric heterochromatin, suggesting a role in its assembly. Here we demonstrate that depletion of the catalytic ATPase subunit CHD4/Mi-2β in cells with a dampened DNA damage response results in a slow-growth phenotype characterized by delayed progression through S phase. Furthermore, we observe defects in pericentric heterochromatin maintenance and assembly. Our data suggest that chromatin assembly defects are sensed by an ATM-dependent intra–S phase chromatin quality checkpoint, resulting in a temporal block to the transition from early to late S phase. These findings implicate Mi-2β in the maintenance of chromatin structure and proper cell cycle progression. |
format | Online Article Text |
id | pubmed-3164457 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-31644572011-11-16 Mi-2/NuRD complex function is required for normal S phase progression and assembly of pericentric heterochromatin Sims, Jennifer K. Wade, Paul A. Mol Biol Cell Articles During chromosome duplication, it is essential to replicate not only the DNA sequence, but also the complex nucleoprotein structures of chromatin. Pericentric heterochromatin is critical for silencing repetitive elements and plays an essential structural role during mitosis. However, relatively little is understood about its assembly and maintenance during replication. The Mi2/NuRD chromatin remodeling complex tightly associates with actively replicating pericentric heterochromatin, suggesting a role in its assembly. Here we demonstrate that depletion of the catalytic ATPase subunit CHD4/Mi-2β in cells with a dampened DNA damage response results in a slow-growth phenotype characterized by delayed progression through S phase. Furthermore, we observe defects in pericentric heterochromatin maintenance and assembly. Our data suggest that chromatin assembly defects are sensed by an ATM-dependent intra–S phase chromatin quality checkpoint, resulting in a temporal block to the transition from early to late S phase. These findings implicate Mi-2β in the maintenance of chromatin structure and proper cell cycle progression. The American Society for Cell Biology 2011-09-01 /pmc/articles/PMC3164457/ /pubmed/21737684 http://dx.doi.org/10.1091/mbc.E11-03-0258 Text en This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Sims, Jennifer K. Wade, Paul A. Mi-2/NuRD complex function is required for normal S phase progression and assembly of pericentric heterochromatin |
title | Mi-2/NuRD complex function is required for normal S phase progression and assembly of pericentric heterochromatin |
title_full | Mi-2/NuRD complex function is required for normal S phase progression and assembly of pericentric heterochromatin |
title_fullStr | Mi-2/NuRD complex function is required for normal S phase progression and assembly of pericentric heterochromatin |
title_full_unstemmed | Mi-2/NuRD complex function is required for normal S phase progression and assembly of pericentric heterochromatin |
title_short | Mi-2/NuRD complex function is required for normal S phase progression and assembly of pericentric heterochromatin |
title_sort | mi-2/nurd complex function is required for normal s phase progression and assembly of pericentric heterochromatin |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164457/ https://www.ncbi.nlm.nih.gov/pubmed/21737684 http://dx.doi.org/10.1091/mbc.E11-03-0258 |
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