title: Compaction and segregation of sister chromatids via active loop extrusion.
abstract: 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.
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Anton
authors.identifier: 0000-0002-2210-8616
authors.initials: A
authors.lastname: Goloborodko
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Imakaev
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, United States.|Department of Physics and Astronomy, Northwestern University, Evanston, United States.
authors.forename: John F
authors.initials: JF
authors.lastname: Marko
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, United States.|Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Leonid
authors.identifier: 0000-0002-0785-5410
authors.initials: L
authors.lastname: Mirny
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism*; D020090:Chromosome Segregation; D003198:Computer Simulation; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D008540:Meiosis; D008938:Mitosis; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C108312:condensin complexes; D000251:Adenosine Triphosphatases
keywords: biophysics; chromosome; chromosomes; compaction; genes; molecular dynamics; none; polymer; simulations; structural biology