title: 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: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors: Jennifer K
authors: JK
authors: Sims
authors: Paul A
authors: PA
authors: Wade
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D016196:S Phase; D059807:S Phase Cell Cycle Checkpoints; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D001324:Autoantigens; C115323:CHD4 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D006657:Histones; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex