Compaction and segregation of sister chromatids via active loop extrusion

• DOI: 10.7554/elife.14864
• Publication Date: 2016-05-18T11:58:45Z
• Authors: Anton Goloborodko; Maxim V Imakaev; John F Marko; Leonid Mirny
• Keywords: Adenosine Triphosphatases; DNA Replication; 0301 basic medicine; QH301-705.5; polymer; Science; Q; R; Mitosis; Chromatids; Biophysics and Structural Biology; Models, Biological; molecular dynamics; DNA-Binding Proteins; Meiosis; 03 medical and health sciences; Chromosome Segregation; Multiprotein Complexes; Medicine; compaction; Computer Simulation; chromosome; simulations; Biology (General)

The mechanism by which chromatids and chromosomes are segregated during mitosis and meiosis is a major puzzle of biology and biophysics. Using polymer simulations of chromosome dynamics, we show that a single mechanism of loop extrusion by condensins can robustly compact, segregate and disentangle chromosomes, arriving at individualized chromatids with morphology observed in vivo. Our model resolves the paradox of topological simplification concomitant with chromosome 'condensation', and explains how enzymes a few nanometers in size are able to control chromosome geometry and topology at micron length scales. We suggest that loop extrusion is a universal mechanism of genome folding that mediates functional interactions during interphase and compacts chromosomes during mitosis.