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The human CENP-A centromeric nucleosome-associated complex.

Daniel R Foltz·Lars E T Jansen·Ben E Black·Aaron O Bailey·John R Yates·Don W Cleveland
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Abstract

The basic element for chromosome inheritance, the centromere, is epigenetically determined in mammals. The prime candidate for specifying centromere identity is the array of nucleosomes assembled with CENP-A, the centromere-specific histone H3 variant. Here, we show that CENP-A nucleosomes directly recruit a proximal CENP-A nucleosome associated complex (NAC) comprised of three new human centromere proteins (CENP-M, CENP-N and CENP-T), along with CENP-U(50), CENP-C and CENP-H. Assembly of the CENP-A NAC at centromeres is dependent on CENP-M, CENP-N and CENP-T. Facilitates chromatin transcription (FACT) and nucleophosmin-1 (previously implicated in transcriptional chromatin remodelling and as a multifunctional nuclear chaperone, respectively) are absent from histone H3-containing nucleosomes, but are stably recruited to CENP-A nucleosomes independent of CENP-A NAC. Seven new CENP-A-nucleosome distal (CAD) centromere components (CENP-K, CENP-L, CENP-O, CENP-P, CENP-Q, CENP-R and CENP-S) are identified as assembling on the CENP-A NAC. The CENP-A NAC is essential, as disruption of the complex causes errors of chromosome alignment and segregation that preclude cell survival despite continued centromere-derived mitotic checkpoint signalling.

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Amino Acid SequenceAutoantigensCentromereCentromere Protein AChromatin Assembly Factor-1Chromatin Assembly and DisassemblyChromosomal Proteins, Non-HistoneChromosomes, HumanDNA-Binding ProteinsHeLa CellsHistonesHumansMitosisMolecular Sequence DataNucleosomesProtein BindingSignal TransductionJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't

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Daniel R Foltz, Lars E T Jansen, Ben E Black, Aaron O Bailey, John R Yates, Don W Cleveland. 2006-04-16. The human CENP-A centromeric nucleosome-associated complex.. https://doi.org/10.1038/ncb1397

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