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
|
リソース情報 |
酵母 |
FYP2132(GST-spCENP-A) |