Heterochromatin links to centromeric protection by recruiting shugoshin

Nature. 2008 Sep 11;455(7210):251-5. doi: 10.1038/nature07217.

Abstract

The centromere of a chromosome is composed mainly of two domains, a kinetochore assembling core centromere and peri-centromeric heterochromatin regions. The crucial role of centromeric heterochromatin is still unknown, because even in simpler unicellular organisms such as the fission yeast Schizosaccharomyces pombe, the heterochromatin protein Swi6 (HP1 homologue) has several functions at centromeres, including silencing gene expression and recombination, enriching cohesin, promoting kinetochore assembly, and, ultimately, preventing erroneous microtubule attachment to the kinetochores. Here we show that the requirement of heterochromatin for mitotic chromosome segregation is largely replaced by forcibly enriching cohesin at centromeres in fission yeast. However, this enrichment of cohesin is not sufficient to replace the meiotic requirement for heterochromatin. We find that the heterochromatin protein Swi6 associates directly with meiosis-specific shugoshin Sgo1, a protector of cohesin at centromeres. A point mutation of Sgo1 (V242E), which abolishes the interaction with Swi6, impairs the centromeric localization and function of Sgo1. The forced centromeric localization of Sgo1 restores proper meiotic chromosome segregation in swi6 cells. We also show that the direct link between HP1 and shugoshin is conserved in human cells. Taken together, our findings suggest that the recruitment of shugoshin is the important primary role for centromeric heterochromatin in ensuring eukaryotic chromosome segregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Centromere / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Segregation
  • Heterochromatin / metabolism*
  • Humans
  • Meiosis
  • Mitosis
  • Protein Binding
  • Protein Transport
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • SGO1 protein, human
  • Schizosaccharomyces pombe Proteins
  • Sgo1 protein, S pombe
  • Swi6 protein, S pombe
  • cohesins
  • heterochromatin-specific nonhistone chromosomal protein HP-1