Monopolin recruits condensin to organize centromere DNA and repetitive DNA sequences

Mol Biol Cell. 2013 Sep;24(18):2807-19. doi: 10.1091/mbc.E13-05-0229. Epub 2013 Jul 24.

Abstract

The establishment and maintenance of higher-order structure at centromeres is essential for accurate chromosome segregation. The monopolin complex is thought to cross-link multiple kinetochore complexes to prevent merotelic attachments that result in chromosome missegregation. This model is based on structural analysis and the requirement that monopolin execute mitotic and meiotic chromosome segregation in Schizosaccharomyces pombe, which has more than one kinetochore-microtubule attachment/centromere, and co-orient sister chromatids in meiosis I in Saccharomyces cerevisiae. Recent data from S. pombe suggest an alternative possibility: that the recruitment of condensin is the primary function of monopolin. Here we test these models using the yeast Candida albicans. C. albicans cells lacking monopolin exhibit defects in chromosome segregation, increased distance between centromeres, and decreased stability of several types of repeat DNA. Of note, changing kinetochore-microtubule copy number from one to more than one kinetochore-microtubule/centromere does not alter the requirement for monopolin. Furthermore, monopolin recruits condensin to C. albicans centromeres, and overexpression of condensin suppresses chromosome segregation defects in strains lacking monopolin. We propose that the key function of monopolin is to recruit condensin in order to promote the assembly of higher-order structure at centromere and repetitive DNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Candida albicans / cytology
  • Candida albicans / genetics
  • Candida albicans / metabolism*
  • Cell Cycle
  • Centromere / metabolism*
  • Chromosome Segregation / genetics
  • Chromosomes, Fungal / metabolism
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism*
  • DNA, Ribosomal / genetics
  • DNA-Binding Proteins / metabolism*
  • Fungal Proteins / metabolism*
  • Gene Deletion
  • Genome, Fungal
  • Kinetochores / metabolism
  • Metaphase
  • Microtubules / metabolism
  • Models, Biological
  • Multiprotein Complexes / metabolism*
  • Protein Transport
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Spindle Apparatus / metabolism

Substances

  • DNA, Fungal
  • DNA, Ribosomal
  • DNA-Binding Proteins
  • Fungal Proteins
  • Multiprotein Complexes
  • condensin complexes
  • Adenosine Triphosphatases