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Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in fission yeast

Centromeric identity and chromosome segregation are determined by the precise centromeric targeting of CENP-A, the centromere-specific histone H3 variant. The significance of the amino-terminal domain (NTD) of CENP-A in this process remains unclear. Here, we assessed the functional significance of e...

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Autores principales: Tan, Hwei Ling, Lim, Kim Kiat, Yang, Qiaoyun, Fan, Jing-Song, Sayed, Ahmed Mahmoud Mohammed, Low, Liy Sim, Ren, Bingbing, Lim, Teck Kwang, Lin, Qingsong, Mok, Yu-Keung, Liou, Yih-Cherng, Chen, Ee Sin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814953/
https://www.ncbi.nlm.nih.gov/pubmed/29194511
http://dx.doi.org/10.1093/nar/gkx1180
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author Tan, Hwei Ling
Lim, Kim Kiat
Yang, Qiaoyun
Fan, Jing-Song
Sayed, Ahmed Mahmoud Mohammed
Low, Liy Sim
Ren, Bingbing
Lim, Teck Kwang
Lin, Qingsong
Mok, Yu-Keung
Liou, Yih-Cherng
Chen, Ee Sin
author_facet Tan, Hwei Ling
Lim, Kim Kiat
Yang, Qiaoyun
Fan, Jing-Song
Sayed, Ahmed Mahmoud Mohammed
Low, Liy Sim
Ren, Bingbing
Lim, Teck Kwang
Lin, Qingsong
Mok, Yu-Keung
Liou, Yih-Cherng
Chen, Ee Sin
author_sort Tan, Hwei Ling
collection PubMed
description Centromeric identity and chromosome segregation are determined by the precise centromeric targeting of CENP-A, the centromere-specific histone H3 variant. The significance of the amino-terminal domain (NTD) of CENP-A in this process remains unclear. Here, we assessed the functional significance of each residue within the NTD of CENP-A from Schizosaccharomyces pombe (SpCENP-A) and identified a proline-rich ‘GRANT’ (Genomic stability-Regulating site within CENP-A N-Terminus) motif that is important for CENP-A function. Through sequential mutagenesis, we show that GRANT proline residues are essential for coordinating SpCENP-A centromeric targeting. GRANT proline-15 (P15), in particular, undergoes cis–trans isomerization to regulate chromosome segregation fidelity, which appears to be carried out by two FK506-binding protein (FKBP) family prolyl cis–trans isomerases. Using proteomics analysis, we further identified the SpCENP-A-localizing chaperone Sim3 as a SpCENP-A NTD interacting protein that is dependent on GRANT proline residues. Ectopic expression of sim3(+) complemented the chromosome segregation defect arising from the loss of these proline residues. Overall, cis–trans proline isomerization is a post-translational modification of the SpCENP-A NTD that confers precise propagation of centromeric integrity in fission yeast, presumably via targeting SpCENP-A to the centromere.
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spelling pubmed-58149532018-02-23 Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in fission yeast Tan, Hwei Ling Lim, Kim Kiat Yang, Qiaoyun Fan, Jing-Song Sayed, Ahmed Mahmoud Mohammed Low, Liy Sim Ren, Bingbing Lim, Teck Kwang Lin, Qingsong Mok, Yu-Keung Liou, Yih-Cherng Chen, Ee Sin Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Centromeric identity and chromosome segregation are determined by the precise centromeric targeting of CENP-A, the centromere-specific histone H3 variant. The significance of the amino-terminal domain (NTD) of CENP-A in this process remains unclear. Here, we assessed the functional significance of each residue within the NTD of CENP-A from Schizosaccharomyces pombe (SpCENP-A) and identified a proline-rich ‘GRANT’ (Genomic stability-Regulating site within CENP-A N-Terminus) motif that is important for CENP-A function. Through sequential mutagenesis, we show that GRANT proline residues are essential for coordinating SpCENP-A centromeric targeting. GRANT proline-15 (P15), in particular, undergoes cis–trans isomerization to regulate chromosome segregation fidelity, which appears to be carried out by two FK506-binding protein (FKBP) family prolyl cis–trans isomerases. Using proteomics analysis, we further identified the SpCENP-A-localizing chaperone Sim3 as a SpCENP-A NTD interacting protein that is dependent on GRANT proline residues. Ectopic expression of sim3(+) complemented the chromosome segregation defect arising from the loss of these proline residues. Overall, cis–trans proline isomerization is a post-translational modification of the SpCENP-A NTD that confers precise propagation of centromeric integrity in fission yeast, presumably via targeting SpCENP-A to the centromere. Oxford University Press 2018-02-16 2017-11-29 /pmc/articles/PMC5814953/ /pubmed/29194511 http://dx.doi.org/10.1093/nar/gkx1180 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Tan, Hwei Ling
Lim, Kim Kiat
Yang, Qiaoyun
Fan, Jing-Song
Sayed, Ahmed Mahmoud Mohammed
Low, Liy Sim
Ren, Bingbing
Lim, Teck Kwang
Lin, Qingsong
Mok, Yu-Keung
Liou, Yih-Cherng
Chen, Ee Sin
Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in fission yeast
title Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in fission yeast
title_full Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in fission yeast
title_fullStr Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in fission yeast
title_full_unstemmed Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in fission yeast
title_short Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in fission yeast
title_sort prolyl isomerization of the cenp-a n-terminus regulates centromeric integrity in fission yeast
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814953/
https://www.ncbi.nlm.nih.gov/pubmed/29194511
http://dx.doi.org/10.1093/nar/gkx1180
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