Mi-2/NuRD complex function is required for normal S phase progression and assembly of pericentric heterochromatin.

Abstract	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.
Authors	Jennifer K Sims, Paul A Wade
Journal	Molecular biology of the cell (Mol Biol Cell) Vol. 22 Issue 17 Pg. 3094-102 (Sep 2011) ISSN: 1939-4586 [Electronic] United States
PMID	21737684 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
Chemical References	Autoantigens CHD4 protein, human Cell Cycle Proteins DNA-Binding Proteins Heterochromatin Histones Tumor Suppressor Proteins ATM protein, human Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases Mi-2 Nucleosome Remodeling and Deacetylase Complex
Topics	Ataxia Telangiectasia Mutated Proteins Autoantigens (genetics, metabolism) Cell Cycle Proteins (metabolism) Cell Line Cell Proliferation DNA-Binding Proteins (metabolism) Gene Knockdown Techniques Heterochromatin (metabolism) Histones (metabolism) Humans Mi-2 Nucleosome Remodeling and Deacetylase Complex (genetics, metabolism) Microscopy, Fluorescence Phosphorylation Protein Serine-Threonine Kinases (metabolism) RNA Interference S Phase S Phase Cell Cycle Checkpoints Tumor Suppressor Proteins (metabolism)

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