論文 - 詳細
| RRC ID | 49621 |
|---|---|
| 著者 | Tan HL, Lim KK, Yang Q, Fan JS, Sayed AMM, Low LS, Ren B, Lim TK, Lin Q, Mok YK, Liou YC, Chen ES. |
| タイトル | Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in fission yeast. |
| ジャーナル | Nucleic Acids Res |
| 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. |
| 巻・号 | 46(3) |
| ページ | 1167-1179 |
| 公開日 | 2018-2-16 |
| DOI | 10.1093/nar/gkx1180 |
| PII | 4670952 |
| PMID | 29194511 |
| PMC | PMC5814953 |
| MeSH | Amino Acid Motifs Centromere / metabolism* Centromere / ultrastructure Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism* Chromosome Segregation Chromosomes, Fungal / chemistry Chromosomes, Fungal / metabolism* Genetic Complementation Test Genomic Instability Isomerism Kinetics Nuclear Proteins / genetics Nuclear Proteins / metabolism* Proline / chemistry Proline / metabolism* Protein Isoforms / genetics Protein Isoforms / metabolism Protein Processing, Post-Translational* Schizosaccharomyces / genetics Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Sequence Alignment Tacrolimus Binding Proteins / genetics Tacrolimus Binding Proteins / metabolism |
| IF | 11.502 |
| 引用数 | 3 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 酵母 | FYP2132(GST-spCENP-A) |