Establishment of sister chromatid cohesion at the S. cerevisiae replication fork

Mol Cell. 2006 Sep 15;23(6):787-99. doi: 10.1016/j.molcel.2006.08.018. Epub 2006 Sep 7.


Two identical sister copies of eukaryotic chromosomes are synthesized during S phase. To facilitate their recognition as pairs for segregation in mitosis, sister chromatids are held together from their synthesis onward by the chromosomal cohesin complex. Replication fork progression is thought to be coupled to establishment of sister chromatid cohesion, facilitating identification of replication products, but evidence for this has remained circumstantial. Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks. The ring-shaped cohesin complex is loaded onto chromosomes before S phase in an ATP hydrolysis-dependent reaction. Cohesion establishment during DNA replication follows without further cohesin recruitment and without need for cohesin to re-engage an ATP hydrolysis motif that is critical for its initial DNA binding. This provides evidence for cohesion establishment in the context of replication forks and imposes constraints on the mechanism involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / analysis
  • Acetyltransferases / metabolism
  • Acetyltransferases / physiology
  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism
  • Amino Acid Motifs / physiology
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / metabolism
  • Chromatids / metabolism*
  • Chromosomal Proteins, Non-Histone / analysis
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cohesins
  • DNA Replication / physiology*
  • DNA, Fungal / biosynthesis
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology
  • Models, Genetic
  • Nuclear Proteins / analysis
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology
  • Proliferating Cell Nuclear Antigen / metabolism
  • S Phase / physiology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / analysis
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology


  • CTF18 protein, S cerevisiae
  • CTF4 protein, S cerevisiae
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA, Fungal
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Proliferating Cell Nuclear Antigen
  • Saccharomyces cerevisiae Proteins
  • Acetyltransferases
  • ECO1 protein, S cerevisiae
  • Adenosine Triphosphatases

Associated data

  • OMIM/GSE5719