The kinetochore is an enhancer of pericentric cohesin binding

PLoS Biol. 2004 Sep;2(9):E260. doi: 10.1371/journal.pbio.0020260. Epub 2004 Jul 27.

Abstract

The recruitment of cohesins to pericentric chromatin in some organisms appears to require heterochromatin associated with repetitive DNA. However, neocentromeres and budding yeast centromeres lack flanking repetitive DNA, indicating that cohesin recruitment occurs through an alternative pathway. Here, we demonstrate that all budding yeast chromosomes assemble cohesin domains that extend over 20-50 kb of unique pericentric sequences flanking the conserved 120-bp centromeric DNA. The assembly of these cohesin domains requires the presence of a functional kinetochore in every cell cycle. A similar enhancement of cohesin binding was also observed in regions flanking an ectopic centromere. At both endogenous and ectopic locations, the centromeric enhancer amplified the inherent levels of cohesin binding that are unique to each region. Thus, kinetochores are enhancers of cohesin association that act over tens of kilobases to assemble pericentric cohesin domains. These domains are larger than the pericentric regions stretched by microtubule attachments, and thus are likely to counter microtubule-dependent forces. Kinetochores mediate two essential segregation functions: chromosome movement through microtubule attachment and biorientation of sister chromatids through the recruitment of high levels of cohesin to pericentric regions. We suggest that the coordination of chromosome movement and biorientation makes the kinetochore an autonomous segregation unit.

Publication types

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

MeSH terms

  • Blotting, Southern
  • Cell Cycle
  • Cell Cycle Proteins / chemistry*
  • Cells, Cultured
  • Centromere / chemistry
  • Centromere / ultrastructure
  • Chondroitin Sulfate Proteoglycans / chemistry
  • Chromatin Immunoprecipitation
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomes / ultrastructure
  • Cohesins
  • DNA / chemistry
  • Enhancer Elements, Genetic
  • Fungal Proteins / chemistry*
  • Genes, Fungal
  • Genotype
  • Green Fluorescent Proteins / chemistry
  • Immunoprecipitation
  • Kinetochores / chemistry
  • Kinetochores / metabolism*
  • Microtubules / chemistry
  • Mitosis
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry*
  • Oligonucleotide Array Sequence Analysis
  • Open Reading Frames
  • Phosphoproteins / chemistry
  • Protein Binding
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / chemistry
  • Spindle Apparatus

Substances

  • Cell Cycle Proteins
  • Chondroitin Sulfate Proteoglycans
  • Chromosomal Proteins, Non-Histone
  • Fungal Proteins
  • MCD1 protein, S cerevisiae
  • Nuclear Proteins
  • Phosphoproteins
  • SMC3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Green Fluorescent Proteins
  • DNA