A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1

Nat Cell Biol. 2004 Nov;6(11):1135-41. doi: 10.1038/ncb1187. Epub 2004 Oct 24.


Defects in kinetochore proteins often lead to aneuploidy and cancer. Mis12-Mtw1 is a conserved, essential kinetochore protein family. Here, we show that a Mis12 core complex exists in Schizosaccharomyces pombe and human cells. Nine polypeptides bind to human hMis12; two of these, HEC1 and Zwint-1, are authentic kinetochore proteins. Four other human proteins of unknown function (c20orf172, DC8, PMF1 and KIAA1570) correspond to yeast Mis12-Mtw1 complex components and are shown to be required for chromosome segregation in HeLa cells using RNA interference (RNAi). Surprisingly, hMis12 also forms a stable complex with the centromeric heterochromatin components HP1alpha and HP1gamma. Double HP1 RNAi abolishes kinetochore localization of hMis12 and DC8. Therefore, centromeric HP1 may be the base to anchor the hMis12 core complex that is enriched with coiled coils and extends to outer Zwint-1 during mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Cycle Proteins / genetics*
  • Centromere*
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Heterochromatin / metabolism*
  • Humans
  • Kinetochores / metabolism*
  • Microtubule-Associated Proteins / genetics*
  • Molecular Sequence Data
  • RNA Interference
  • RNA, Fungal
  • Schizosaccharomyces pombe Proteins / genetics*


  • CBX5 protein, human
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • MIS12 protein, human
  • Microtubule-Associated Proteins
  • RNA, Fungal
  • Schizosaccharomyces pombe Proteins
  • mis12 protein, S pombe
  • Chromobox Protein Homolog 5

Associated data

  • GENBANK/AB046790
  • GENBANK/AF255793
  • GENBANK/BC033656
  • GENBANK/BC058899