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Title: Prolyl isomerization of the CENP-A N-Terminus regulates centromeric integrity in fission yeast
Authors: Tan, H.L. 
Lim, K.K. 
Yang, Q. 
Fan, J.-S. 
Sayed, A.M.M.
Low, L.S. 
Ren, B. 
Lim, T.K. 
Lin, Q. 
Mok, Y.-K. 
Liou, Y.-C. 
Chen, E.S. 
Issue Date: 2018
Publisher: Oxford University Press
Citation: Tan, H.L., Lim, K.K., Yang, Q., Fan, J.-S., Sayed, A.M.M., Low, L.S., Ren, B., Lim, T.K., Lin, Q., Mok, Y.-K., Liou, Y.-C., Chen, E.S. (2018). Prolyl isomerization of the CENP-A N-Terminus regulates centromeric integrity in fission yeast. Nucleic Acids Research 46 (3) : 1167-1179. ScholarBank@NUS Repository.
Rights: Attribution-NonCommercial 4.0 International
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 fromSchizosaccharomyces 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-transisomerization 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 posttranslational modification of the SpCENP-A NTD that confers precise propagation of centromeric integrity in fission yeast, presumably via targeting SpCENP-A to the centromere. © The Author(s) 2017.
Source Title: Nucleic Acids Research
ISSN: 0305-1048
DOI: 10.1093/nar/gkx1180
Rights: Attribution-NonCommercial 4.0 International
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