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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

483 Scopus citations

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), CENPC 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.

Original languageEnglish (US)
Pages (from-to)458-469
Number of pages12
JournalNature Cell Biology
Volume8
Issue number5
DOIs
StatePublished - May 2006

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'The human CENP-A centromeric nucleosome-associated complex'. Together they form a unique fingerprint.

Cite this