The mechanism of sister chromatid cohesion.
Each of our cells inherit their genetic information in the form of chromosomes from a mother cell. In order that we obtain the full genetic complement, cells need to ensure that replicated chromosomes are accurately split and distributed during cell division. Mistakes in this process lead to aneuploidies, cells with supernumerous or missing chromosomes. Most aneuploid human embryos are not viable, and if they are, they develop severe birth defects. Aneuploidies later in human life are frequently found associated with the development of malignant cancer. DNA replication during S-phase is linked to segregation of the sister copies in mitosis by sister chromatid cohesion. A chromosomal protein complex, cohesin, holds replicated sister DNA strands together after their synthesis. This allows pairs of replication products to be recognised by the spindle apparatus in mitosis for segregation into opposite direction. At anaphase onset, cohesin is destroyed by a site-specific protease, separase. Here I review what we have learned about the molecular mechanism of sister chromatid cohesion. Cohesin forms a large proteinaceous ring that may hold sister chromatids by encircling and topological trapping. To understand how cohesin links newly synthesised replication products, biochemical assays to study the enzymology of cohesin will be required.
Uhlmann
Frank
F
Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, UK. frank.uhlmann@cancer.org.uk
D000818:Animals; D018797:Cell Cycle Proteins; D002455:Cell Division; D002842:Chromatids / Q000378:metabolism / Q000648:ultrastructure*; D002868:Chromosomal Proteins, Non-Histone; D020090:Chromosome Segregation; D004261:DNA Replication; D005656:Fungal Proteins; D006801:Humans; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism; D008941:Spindle Apparatus; D015003:Yeasts; D000097722:Cohesins
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D005656:Fungal Proteins; D009687:Nuclear Proteins; D000097722:Cohesins