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 SpCENPA
NTD interacting protein that is dependent on
GRANT proline residues. Ectopic expression of
sim3+ complemented the chromosome segregation
defect arising fromthe 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.
Research Abstract
Research Department
Research Journal
Nucleic acids research
Research Member
Research Publisher
Oxford University Press
Research Rank
1
Research Vol
NULL
Research Website
NULL
Research Year
2018
Research Pages
NULL