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


ABSTRACT: 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.

SUBMITTER: Tan HL 

PROVIDER: S-EPMC5814953 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Tan Hwei Ling HL   Lim Kim Kiat KK   Yang Qiaoyun Q   Fan Jing-Song JS   Sayed Ahmed Mahmoud Mohammed AMM   Low Liy Sim LS   Ren Bingbing B   Lim Teck Kwang TK   Lin Qingsong Q   Mok Yu-Keung YK   Liou Yih-Cherng YC   Chen Ee Sin ES  

Nucleic acids research 20180201 3


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 importan  ...[more]

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2013-03-14 | GSE44206 | GEO