The human CENP-A centromeric nucleosome-associated complex

Author: Foltz, D.R.; Jansen, L.E.T.; Black, B.E.; Bailey, A.O.; Yates, J.R. 3rd; Cleveland, D.W.

Description: 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.

Subject headings: Amino Acid Sequence; Autoantigens–chemistry, isolation & purification; metabolism; Centromere–metabolism; Chromatin Assembly Factor-1; Chromatin Assembly and Disassembly–genetics; Chromosomal Proteins, Non-Histone–chemistry, isolation & purification, metabolism; Chromosomes, Human genetics; DNA-Binding Proteins–metabolism; HeLa Cells; Histones–chemistry; Humans; Mitosis–genetics; Molecular Sequence Data; Nucleosomes–metabolism; Protein Binding; Signal Transduction

Publication year: 2006

Journal or book title: Nature Cell Biology

Volume: 8

Issue: 5

Pages: 458-469

Find the full text:

Find more like this one (cited by):,16&hl=en

Type: Journal Article

Serial number: 13