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

doi:10.1073/pnas.1302955110

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

50 Citations (Scopus)

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 language	English
Pages (from-to)	8579-8584
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	110
Issue number	21
DOIs	https://doi.org/10.1073/pnas.1302955110
Publication status	Published - 21 May 2013
Externally published	Yes

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@article{07661bef63174bd4a8fad8bcfd798b5c,

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

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.",

author = "Damien Goutte-Gattat and Muhammad Shuaib and Khalid Ouararhni and Thierry Gautier and Skoufias, \{Dimitrios A.\} and Ali Hamiche and Stefan Dimitrov",

year = "2013",

month = may,

day = "21",

doi = "10.1073/pnas.1302955110",

language = "English",

volume = "110",

pages = "8579--8584",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Goutte-Gattat, D, Shuaib, M, Ouararhni, K, Gautier, T, Skoufias, DA, Hamiche, A & Dimitrov, S 2013, 'Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function', Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 21, pp. 8579-8584. https://doi.org/10.1073/pnas.1302955110

Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function. / Goutte-Gattat, Damien; Shuaib, Muhammad; Ouararhni, Khalid et al.
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 journal › Article › peer-review

TY - JOUR

T1 - Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function

AU - Goutte-Gattat, Damien

AU - Shuaib, Muhammad

AU - Ouararhni, Khalid

AU - Gautier, Thierry

AU - Skoufias, Dimitrios A.

AU - Hamiche, Ali

AU - Dimitrov, Stefan

PY - 2013/5/21

Y1 - 2013/5/21

N2 - 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.

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.

UR - https://www.scopus.com/pages/publications/84878140645

U2 - 10.1073/pnas.1302955110

DO - 10.1073/pnas.1302955110

M3 - Article

C2 - 23657009

AN - SCOPUS:84878140645

SN - 0027-8424

VL - 110

SP - 8579

EP - 8584

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 21

ER -

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

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