Repeat-Associated Fission Yeast-Like Regional Centromeres in the Ascomycetous Budding Yeast Candida tropicalis

PLoS Genet. 2016 Feb 4;12(2):e1005839. doi: 10.1371/journal.pgen.1005839. eCollection 2016 Feb.


The centromere, on which kinetochore proteins assemble, ensures precise chromosome segregation. Centromeres are largely specified by the histone H3 variant CENP-A (also known as Cse4 in yeasts). Structurally, centromere DNA sequences are highly diverse in nature. However, the evolutionary consequence of these structural diversities on de novo CENP-A chromatin formation remains elusive. Here, we report the identification of centromeres, as the binding sites of four evolutionarily conserved kinetochore proteins, in the human pathogenic budding yeast Candida tropicalis. Each of the seven centromeres comprises a 2 to 5 kb non-repetitive mid core flanked by 2 to 5 kb inverted repeats. The repeat-associated centromeres of C. tropicalis all share a high degree of sequence conservation with each other and are strikingly diverged from the unique and mostly non-repetitive centromeres of related Candida species--Candida albicans, Candida dubliniensis, and Candida lusitaniae. Using a plasmid-based assay, we further demonstrate that pericentric inverted repeats and the underlying DNA sequence provide a structural determinant in CENP-A recruitment in C. tropicalis, as opposed to epigenetically regulated CENP-A loading at centromeres in C. albicans. Thus, the centromere structure and its influence on de novo CENP-A recruitment has been significantly rewired in closely related Candida species. Strikingly, the centromere structural properties along with role of pericentric repeats in de novo CENP-A loading in C. tropicalis are more reminiscent to those of the distantly related fission yeast Schizosaccharomyces pombe. Taken together, we demonstrate, for the first time, fission yeast-like repeat-associated centromeres in an ascomycetous budding yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / metabolism
  • Base Pairing / genetics
  • Candida tropicalis / genetics*
  • Centromere / genetics*
  • Centromere Protein A
  • Chromatin Immunoprecipitation
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Mapping
  • Chromosome Segregation / genetics
  • Chromosomes, Fungal / metabolism
  • Conserved Sequence
  • Evolution, Molecular
  • Gene Rearrangement / genetics
  • Genome, Fungal
  • Inverted Repeat Sequences / genetics
  • Kinetochores / metabolism
  • Mitosis
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Schizosaccharomyces / genetics
  • Species Specificity


  • Autoantigens
  • CENPA protein, human
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • centromere protein C

Grants and funding

This work is supported by a grant from DBT (Grant number: BT/PR14840/BRB/10/880/2010), Govt. of India and intramural funding of JNCASR to KS. RS acknowledges the PRISM project funded by DAE at his institution. GC was a senior research fellow of CSIR, Govt. of India, SRS is a senior research fellow supported by JNCASR and KG acknowledges SPM fellowship from CSIR, Govt. of India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.