Intermolecular DNA interactions stimulated by the cohesin complex in vitro: implications for sister chromatid cohesion

Curr Biol. 2001 Feb 20;11(4):268-72. doi: 10.1016/s0960-9822(01)00066-5.


The establishment of sister chromatid cohesion during S phase and its dissolution at the metaphase-anaphase transition are essential for the faithful segregation of chromosomes in mitosis [1-4]. Recent studies in yeast genetics and Xenopus biochemistry have identified a large protein complex, cohesin, that plays a key role in sister chromatid cohesion [5-10]. The cohesin complex consists of a heterodimeric pair of SMC (structural maintenance of chromosomes) subunits and at least two non-SMC subunits. This structural organization is reminiscent of that of condensin, another major SMC protein complex that drives chromosome condensation in eukaryotic cells [11]. Condensin has been shown to reconfigure and compact DNA in vitro by utilizing the energy of ATP hydrolysis [12]. Very little is known, however, about how cohesin works at a mechanistic level. Here we report the first set of biochemical activities associated with an intact cohesin complex purified from HeLa cell extracts. The cohesin complex binds directly to double-stranded DNA and induces the formation of large protein-DNA aggregates. In the presence of topoisomerase II, cohesin stimulates intermolecular catenation of circular DNA molecules. This activity is in striking contrast to intramolecular knotting directed by condensin [13]. Cohesin also increases the probability of intermolecular ligation of linear DNA molecules in the presence of DNA ligase. Our results are consistent with a model in which cohesin functions as an intermolecular DNA crosslinker and is part of the molecular "glue" that holds sister chromatids together [14].

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / isolation & purification
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Cell Cycle Proteins
  • Chromatids / physiology*
  • Chromosomal Proteins, Non-Histone
  • DNA / metabolism*
  • DNA Ligases / metabolism
  • DNA, Circular / metabolism
  • DNA, Superhelical / metabolism
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins
  • HeLa Cells
  • Humans
  • Multiprotein Complexes
  • Nuclear Proteins / isolation & purification
  • Nuclear Proteins / metabolism*
  • Xenopus laevis


  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA, Circular
  • DNA, Superhelical
  • DNA-Binding Proteins
  • Fungal Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • cohesins
  • condensin complexes
  • Adenosine Triphosphate
  • DNA
  • Adenosine Triphosphatases
  • DNA Ligases