RRC ID 49621
Author Tan HL, Lim KK, Yang Q, Fan JS, Sayed AMM, Low LS, Ren B, Lim TK, Lin Q, Mok YK, Liou YC, Chen ES.
Title Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in fission yeast.
Journal 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.
Volume 46(3)
Pages 1167-1179
Published 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 11.147
Times Cited 3
Resource
Yeast FYP2132(GST-spCENP-A)