Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function

Damien Goutte-Gattat, Muhammad Shuaib, Khalid Ouararhni, Thierry Gautier, Dimitrios A. Skoufias, Ali Hamiche, Stefan Dimitrov

Research output: Contribution to journalArticle

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Abstract

The role of the mitotic phosphorylation of the amino (NH2) terminus of Centromere Protein A (CENP-A), the histone variant epigenetic centromeric marker, remains elusive. Here, we show that the NH2 terminus of human CENP-A is essential for mitotic progression and that localizationof CENP-C, another key centromeric protein, requires only phosphorylation of the CENP-A NH2 terminus, and is independent of the CENP-A NH2 terminus length and amino acid sequence. Mitotic CENP-Anucleosomal complexes containCENP-Candphosphobinding 14-3-3 proteins. In contrast, mitotic nucleosomal complexes carryingnonphosphorylatable CENP-A-S7Acontainedonly lowlevels of CENP-C and no detectable 14-3-3 proteins. Direct interactions betweenthephosphorylatedformofCENP- Aand14-3-3proteinsaswell as between 14-3-3 proteins and CENP-C were demonstrated. Taken together, our results reveal that 14-3-3 proteins could act as specific mitotic "bridges," linking phosphorylated CENP-A and CENP-C,which are necessary for the platform function of CENP-A centromeric chromatin in the assembly and maintenance of active kinetochores.

Original languageEnglish
Pages (from-to)8579-8584
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number21
DOIs
Publication statusPublished - 21 May 2013
Externally publishedYes

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Kinetochores
Chromatin
14-3-3 Proteins
Phosphorylation
Chromatin Assembly and Disassembly
Protein C
centromere protein A
Epigenomics
Histones
Amino Acid Sequence
Maintenance
centromere protein C

ASJC Scopus subject areas

  • General

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Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function. / Goutte-Gattat, Damien; Shuaib, Muhammad; Ouararhni, Khalid; Gautier, Thierry; Skoufias, Dimitrios A.; Hamiche, Ali; Dimitrov, Stefan.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 21, 21.05.2013, p. 8579-8584.

Research output: Contribution to journalArticle

Goutte-Gattat, Damien ; Shuaib, Muhammad ; Ouararhni, Khalid ; Gautier, Thierry ; Skoufias, Dimitrios A. ; Hamiche, Ali ; Dimitrov, Stefan. / Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 21. pp. 8579-8584.
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AB - The role of the mitotic phosphorylation of the amino (NH2) terminus of Centromere Protein A (CENP-A), the histone variant epigenetic centromeric marker, remains elusive. Here, we show that the NH2 terminus of human CENP-A is essential for mitotic progression and that localizationof CENP-C, another key centromeric protein, requires only phosphorylation of the CENP-A NH2 terminus, and is independent of the CENP-A NH2 terminus length and amino acid sequence. Mitotic CENP-Anucleosomal complexes containCENP-Candphosphobinding 14-3-3 proteins. In contrast, mitotic nucleosomal complexes carryingnonphosphorylatable CENP-A-S7Acontainedonly lowlevels of CENP-C and no detectable 14-3-3 proteins. Direct interactions betweenthephosphorylatedformofCENP- Aand14-3-3proteinsaswell as between 14-3-3 proteins and CENP-C were demonstrated. Taken together, our results reveal that 14-3-3 proteins could act as specific mitotic "bridges," linking phosphorylated CENP-A and CENP-C,which are necessary for the platform function of CENP-A centromeric chromatin in the assembly and maintenance of active kinetochores.

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