Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Sims, Jennifer K., Wade, Paul A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
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
_version_ 1782211041657094144
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
work_keys_str_mv AT simsjenniferk mi2nurdcomplexfunctionisrequiredfornormalsphaseprogressionandassemblyofpericentricheterochromatin
AT wadepaula mi2nurdcomplexfunctionisrequiredfornormalsphaseprogressionandassemblyofpericentricheterochromatin