The human CENP-A centromeric nucleosome-associated complex
Copyright policy )The human CENP-A centromeric nucleosome-associated complex
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.
- University of California, San Diego United States
- Scripps Research Institute United States
- Ludwig Cancer Research United States
- University of California, San Diego United States
Chromosomal Proteins, Non-Histone, Centromere, Molecular Sequence Data, Mitosis, Chromatin Assembly and Disassembly, Autoantigens, Nucleosomes, DNA-Binding Proteins, Histones, Chromatin Assembly Factor-1, Chromosomes, Human, Humans, Amino Acid Sequence, Centromere Protein A, HeLa Cells, Protein Binding, Signal Transduction
Chromosomal Proteins, Non-Histone, Centromere, Molecular Sequence Data, Mitosis, Chromatin Assembly and Disassembly, Autoantigens, Nucleosomes, DNA-Binding Proteins, Histones, Chromatin Assembly Factor-1, Chromosomes, Human, Humans, Amino Acid Sequence, Centromere Protein A, HeLa Cells, Protein Binding, Signal Transduction
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