Functional Coupling between DNA Replication and Sister Chromatid Cohesion Establishment

Int J Mol Sci. 2021 Mar 10;22(6):2810. doi: 10.3390/ijms22062810.


Several lines of evidence suggest the existence in the eukaryotic cells of a tight, yet largely unexplored, connection between DNA replication and sister chromatid cohesion. Tethering of newly duplicated chromatids is mediated by cohesin, an evolutionarily conserved hetero-tetrameric protein complex that has a ring-like structure and is believed to encircle DNA. Cohesin is loaded onto chromatin in telophase/G1 and converted into a cohesive state during the subsequent S phase, a process known as cohesion establishment. Many studies have revealed that down-regulation of a number of DNA replication factors gives rise to chromosomal cohesion defects, suggesting that they play critical roles in cohesion establishment. Conversely, loss of cohesin subunits (and/or regulators) has been found to alter DNA replication fork dynamics. A critical step of the cohesion establishment process consists in cohesin acetylation, a modification accomplished by dedicated acetyltransferases that operate at the replication forks. Defects in cohesion establishment give rise to chromosome mis-segregation and aneuploidy, phenotypes frequently observed in pre-cancerous and cancerous cells. Herein, we will review our present knowledge of the molecular mechanisms underlying the functional link between DNA replication and cohesion establishment, a phenomenon that is unique to the eukaryotic organisms.

Keywords: DNA replication; cell cycle; cohesin; replication proteins; sister chromatid cohesion.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism*
  • Chromatids / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Segregation / physiology*
  • Cohesins
  • DNA Replication / physiology*
  • G1 Phase / physiology*
  • Humans
  • Telophase / physiology*


  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone

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