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Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP.

Cell | May 1, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19410544

The centromere is responsible for accurate chromosome segregation. Mammalian centromeres are specified epigenetically, with all active centromeres containing centromere-specific chromatin in which CENP-A replaces histone H3 within the nucleosome. The proteins responsible for assembly of human CENP-A into centromeric nucleosomes during the G1 phase of the cell cycle are shown here to be distinct from the chromatin assembly factors previously shown to load other histone H3 variants. Here we demonstrate that prenucleosomal CENP-A is complexed with histone H4, nucleophosmin 1, and HJURP. Recruitment of new CENP-A into nucleosomes at replicated centromeres is dependent on HJURP. Recognition by HJURP is mediated through the centromere targeting domain (CATD) of CENP-A, a region that we demonstrated previously to induce a unique conformational rigidity to both the subnucleosomal CENP-A heterotetramer and the corresponding assembled nucleosome. We propose HJURP to be a cell-cycle-regulated CENP-A-specific histone chaperone required for centromeric chromatin assembly.

Pubmed ID: 19410544 RIS Download

Mesh terms: Autoantigens | Cell Line | Centromere | Chromatin Assembly and Disassembly | Chromosomal Proteins, Non-Histone | DNA-Binding Proteins | G1 Phase | Histones | Humans | Nuclear Proteins | Nucleosomes

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Associated grants

  • Agency: NIGMS NIH HHS, Id: F32 GM067401
  • Agency: NIGMS NIH HHS, Id: F32 GM067401-03
  • Agency: NIGMS NIH HHS, Id: R01 GM074150
  • Agency: NIGMS NIH HHS, Id: R01 GM074150-04
  • Agency: NIGMS NIH HHS, Id: R01 GM082989
  • Agency: NIGMS NIH HHS, Id: R01 GM082989-01A1
  • Agency: NIGMS NIH HHS, Id: T32 GM008275

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