Prophase Pathway-Dependent Removal of Cohesin From Human Chromosomes Requires Opening of the Smc3-Scc1 Gate

EMBO J. 2013 Mar 6;32(5):666-76. doi: 10.1038/emboj.2013.7. Epub 2013 Jan 29.

Abstract

Faithful transmission of chromosomes during eukaryotic cell division requires sister chromatids to be paired from their generation in S phase until their separation in M phase. Cohesion is mediated by the cohesin complex, whose Smc1, Smc3 and Scc1 subunits form a tripartite ring that entraps both DNA double strands. Whereas centromeric cohesin is removed in late metaphase by Scc1 cleavage, metazoan cohesin at chromosome arms is displaced already in prophase by proteolysis-independent signalling. Which of the three gates is triggered by the prophase pathway to open has remained enigmatic. Here, we show that displacement of human cohesin from early mitotic chromosomes requires dissociation of Smc3 from Scc1 but no opening of the other two gates. In contrast, loading of human cohesin onto chromatin in telophase occurs through the Smc1-Smc3 hinge. We propose that the use of differently regulated gates for loading and release facilitates unidirectionality of DNA's entry into and exit from the cohesin ring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cells, Cultured
  • Chondroitin Sulfate Proteoglycans / genetics
  • Chondroitin Sulfate Proteoglycans / metabolism*
  • Chromatin / genetics*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomes, Human / genetics*
  • Chromosomes, Human / metabolism
  • DNA / genetics
  • DNA-Binding Proteins
  • Humans
  • Immunoprecipitation
  • Immunosuppressive Agents / pharmacology
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / metabolism
  • Microscopy, Fluorescence
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Prophase / physiology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Tacrolimus Binding Proteins / genetics
  • Tacrolimus Binding Proteins / metabolism

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Chondroitin Sulfate Proteoglycans
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Immunosuppressive Agents
  • Nuclear Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • RAD21 protein, human
  • SMC3 protein, human
  • WAPAL protein, human
  • cohesins
  • structural maintenance of chromosome protein 1
  • DNA
  • TOR Serine-Threonine Kinases
  • Tacrolimus Binding Proteins
  • Sirolimus