Wapl controls the dynamic association of cohesin with chromatin

Cell. 2006 Dec 1;127(5):955-67. doi: 10.1016/j.cell.2006.09.040. Epub 2006 Nov 16.


Cohesin establishes sister-chromatid cohesion from S phase until mitosis or meiosis. To allow chromosome segregation, cohesion has to be dissolved. In vertebrate cells, this process is mediated in part by the protease separase, which destroys a small amount of cohesin, but most cohesin is removed from chromosomes without proteolysis. How this is achieved is poorly understood. Here, we show that the interaction between cohesin and chromatin is controlled by Wapl, a protein implicated in heterochromatin formation and tumorigenesis. Wapl is associated with cohesin throughout the cell cycle, and its depletion blocks cohesin dissociation from chromosomes during the early stages of mitosis and prevents the resolution of sister chromatids until anaphase, which occurs after a delay. Wapl depletion also increases the residence time of cohesin on chromatin in interphase. Our data indicate that Wapl is required to unlock cohesin from a particular state in which it is stably bound to chromatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Chromatids / metabolism
  • Chromatin / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomes, Human / genetics
  • Conserved Sequence
  • Evolution, Molecular
  • Humans
  • Interphase
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / metabolism*
  • Oncogene Proteins / chemistry
  • Oncogene Proteins / metabolism*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Prophase
  • Protein Binding
  • Protein Structure, Secondary
  • Proto-Oncogene Proteins
  • Repetitive Sequences, Amino Acid
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / metabolism
  • Telophase


  • Carrier Proteins
  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • MAU2 protein, human
  • MCD1 protein, S cerevisiae
  • Multiprotein Complexes
  • Nuclear Proteins
  • Oncogene Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • RAD61 protein, S cerevisiae
  • SGO1 protein, human
  • Saccharomyces cerevisiae Proteins
  • WAPL protein, human
  • cohesins