Unified mode of centromeric protection by shugoshin in mammalian oocytes and somatic cells

Nat Cell Biol. 2008 Jan;10(1):42-52. doi: 10.1038/ncb1667. Epub 2007 Dec 16.

Abstract

Reductional chromosome segregation in germ cells, where sister chromatids are pulled to the same pole, accompanies the protection of cohesin at centromeres from separase cleavage. Here, we show that mammalian shugoshin Sgo2 is expressed in germ cells and is solely responsible for the centromeric localization of PP2A and the protection of cohesin Rec8 in oocytes, proving conservation of the mechanism from yeast to mammals. However, this role of Sgo2 contrasts with its mitotic role in protecting centromeric cohesin only from prophase dissociation, but never from anaphase cleavage. We demonstrate that, in somatic cells, shugoshin colocalizes with cohesin in prophase or prometaphase, but their localizations become separate when centromeres are pulled oppositely at metaphase. Remarkably, if tension is artificially removed from the centromeres at the metaphase-anaphase transition, cohesin at the centromeres can be protected from separase cleavage even in somatic cells, as in germ cells. These results argue for a unified view of centromeric protection by shugoshin in mitosis and meiosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cells, Cultured
  • Centromere / metabolism*
  • Chromatids / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cohesins
  • Female
  • Gene Expression Profiling*
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Kinetochores / metabolism
  • Male
  • Metaphase / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mitosis / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oocytes / cytology
  • Oocytes / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sister Chromatid Exchange

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Nuclear Proteins
  • Phosphoproteins
  • RNA, Small Interfering
  • Rec8 protein, mouse
  • shugoshin protein, mouse