PIASgamma is required for faithful chromosome segregation in human cells

PLoS One. 2006 Dec 20;1(1):e53. doi: 10.1371/journal.pone.0000053.

Abstract

Background: The precision of the metaphase-anaphase transition ensures stable genetic inheritance. The spindle checkpoint blocks anaphase onset until the last chromosome biorients at metaphase plate, then the bonds between sister chromatids are removed and disjoined chromatids segregate to the spindle poles. But, how sister separation is triggered is not fully understood.

Principal findings: We identify PIASgamma as a human E3 sumo ligase required for timely and efficient sister chromatid separation. In cells lacking PIASgamma, normal metaphase plates form, but the spindle checkpoint is activated, leading to a prolonged metaphase block. Sister chromatids remain cohered even if cohesin is removed by depletion of hSgo1, because DNA catenations persist at centromeres. PIASgamma-depleted cells cannot properly localize Topoisomerase II at centromeres or in the cores of mitotic chromosomes, providing a functional link between PIASgamma and Topoisomerase II.

Conclusions: PIASgamma directs Topoisomerase II to specific chromosome regions that require efficient removal of DNA catenations prior to anaphase. The lack of this activity activates the spindle checkpoint, protecting cells from non-disjunction. Because DNA catenations persist without PIASgamma in the absence of cohesin, removal of catenations and cohesin rings must be regulated in parallel.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anaphase
  • Aurora Kinases
  • Base Sequence
  • Calcium-Binding Proteins / metabolism
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Centromere / physiology
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Segregation / physiology*
  • Cohesins
  • DNA / chemistry
  • DNA / metabolism
  • DNA Topoisomerases, Type II / metabolism
  • HeLa Cells
  • Humans
  • Mad2 Proteins
  • Metaphase
  • Models, Biological
  • Poly-ADP-Ribose Binding Proteins
  • Protein Inhibitors of Activated STAT / antagonists & inhibitors
  • Protein Inhibitors of Activated STAT / genetics
  • Protein Inhibitors of Activated STAT / physiology*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Repressor Proteins / metabolism

Substances

  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • MAD2L1 protein, human
  • Mad2 Proteins
  • PIAS4 protein, human
  • Poly-ADP-Ribose Binding Proteins
  • Protein Inhibitors of Activated STAT
  • RNA, Small Interfering
  • Repressor Proteins
  • SGO1 protein, human
  • DNA
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • DNA Topoisomerases, Type II