Program in Molecular Medicine
Adenosine Triphosphatases; Animals; Antigens; Autoantigens; COS Cells; Centrosome; Cercopithecus aethiops; *Chromatin Assembly and Disassembly; Cytokinesis; DNA Helicases; Histone Deacetylases; Humans; Mice; Microtubules; Mitosis; Protein Binding; Protein Transport; RNA, Small Interfering
Life Sciences | Medicine and Health Sciences
Pericentrin is an integral centrosomal component that anchors regulatory and structural molecules to centrosomes. In a yeast two-hybrid screen with pericentrin we identified chromodomain helicase DNA-binding protein 4 (CHD4/Mi2beta). CHD4 is part of the multiprotein nucleosome remodeling deacetylase (NuRD) complex. We show that many NuRD components interacted with pericentrin by coimmunoprecipitation and that they localized to centrosomes and midbodies. Overexpression of the pericentrin-binding domain of CHD4 or another family member (CHD3) dissociated pericentrin from centrosomes. Depletion of CHD3, but not CHD4, by RNA interference dissociated pericentrin and gamma-tubulin from centrosomes. Microtubule nucleation/organization, cell morphology, and nuclear centration were disrupted in CHD3-depleted cells. Spindles were disorganized, the majority showing a prometaphase-like configuration. Time-lapse imaging revealed mitotic failure before chromosome segregation and cytokinesis failure. We conclude that pericentrin forms complexes with CHD3 and CHD4, but a distinct CHD3-pericentrin complex is required for centrosomal anchoring of pericentrin/gamma-tubulin and for centrosome integrity.
DOI of Published Version
Mol Biol Cell. 2007 Sep;18(9):3667-80. Epub 2007 Jul 11. Link to article on publisher's site
Molecular biology of the cell
Sillibourne, James; Delaval, Benedicte; Redick, Sambra D.; Sinha, Manisha; and Doxsey, Stephen J., "Chromatin remodeling proteins interact with pericentrin to regulate centrosome integrity" (2007). Open Access Articles. 1322.