Modeling the functions of condensin in chromosome shaping and segregation

The mechanistic details underlying the assembly of rod-shaped chromosomes during mitosis and how they segregate from each other to act as individually mobile units remain largely unknown. Here, we construct a coarse-grained physical model of chromosomal DNA and condensins, a class of large protein complexes that plays key roles in these processes. We assume that condensins have two molecular activities: consecutive loop formation in DNA and inter-condensin attractions. Our simulation demonstrates that both of these activities and their balancing acts are essential for the efficient shaping and segregation of mitotic chromosomes. Our results also demonstrate that the shaping and segregation processes are strongly correlated, implying their mechanistic coupling during mitotic chromosome assembly. Our results highlight the functional importance of inter-condensin attractions in chromosome shaping and segregation.

[1]  W. Austin Elam,et al.  Physical Biology of the Cell , 2014, The Yale Journal of Biology and Medicine.

[2]  Carmay Lim,et al.  A simple biophysical model emulates budding yeast chromosome condensation , 2015, eLife.

[3]  K. Nasmyth THE GENOME : Joining , Resolving , and Separating Sister Chromatids During Mitosis and Meiosis , 2006 .

[4]  U. K. Laemmli,et al.  Chromosome structure: improved immunolabeling for electron microscopy , 2005, Chromosoma.

[5]  J. R. Paulson,et al.  Metaphase chromosome structure: the role of nonhistone proteins. , 1978, Cold Spring Harbor symposia on quantitative biology.

[6]  L. Mirny,et al.  Chromosome Compaction by Active Loop Extrusion , 2016, Biophysical journal.

[7]  Job Dekker,et al.  Organization of the Mitotic Chromosome , 2013, Science.

[8]  Cees Dekker,et al.  The condensin complex is a mechanochemical motor that translocates along DNA , 2017, Science.

[9]  A. Belmont Mitotic chromosome structure and condensation. , 2006, Current opinion in cell biology.

[10]  R. Johnson,et al.  The organization of supercoiled DNA from human chromosomes. , 1979, Journal of cell science.

[11]  M. Olvera de la Cruz,et al.  Precipitation of DNA by polyamines: a polyelectrolyte behavior. , 1998, Biophysical journal.

[12]  D. Gerloff,et al.  Three-dimensional topology of the SMC2/SMC4 subcomplex from chicken condensin I revealed by cross-linking and molecular modelling , 2015, Open Biology.

[13]  J. Marko,et al.  Micromechanical studies of mitotic chromosomes. , 2002, Journal of muscle research and cell motility.

[14]  K. Morikawa,et al.  Comparison of MukB homodimer versus MukBEF complex molecular architectures by electron microscopy reveals a higher-order multimerization. , 2005, Biochemical and biophysical research communications.

[15]  A. Mochizuki,et al.  Controlling segregation speed of entangled polymers by the shapes: A simple model for eukaryotic chromosome segregation. , 2016, Physical review. E.

[16]  W. Earnshaw,et al.  Condensin: Architect of mitotic chromosomes , 2009, Chromosome Research.

[17]  Hans-Jörg Limbach,et al.  ESPResSo - an extensible simulation package for research on soft matter systems , 2006, Comput. Phys. Commun..

[18]  K. Kimura,et al.  ATP-Dependent Positive Supercoiling of DNA by 13S Condensin: A Biochemical Implication for Chromosome Condensation , 1997, Cell.

[19]  Cees Dekker,et al.  Real-time imaging of DNA loop extrusion by condensin , 2018, Science.

[20]  D. Marenduzzo,et al.  A simple model for DNA bridging proteins and bacterial or human genomes: bridging-induced attraction and genome compaction , 2015, Journal of physics. Condensed matter : an Institute of Physics journal.

[21]  T. Hirano,et al.  Real-Time Detection of Single-Molecule DNA Compaction by Condensin I , 2004, Current Biology.

[22]  D. Sherratt,et al.  In Vivo Architecture and Action of Bacterial Structural Maintenance of Chromosome Proteins , 2012, Science.

[23]  土井 正男,et al.  Introduction to polymer physics , 1996 .

[24]  J. Loparo,et al.  Multistep assembly of DNA condensation clusters by SMC , 2016, Nature Communications.

[25]  Micromechanical studies of mitotic chromosomes , 2008, Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology.

[26]  T. Hirano,et al.  Reconstitution of mitotic chromatids with a minimum set of purified factors , 2015, Nature Cell Biology.

[27]  John F. Marko,et al.  Self-organization of domain structures by DNA-loop-extruding enzymes , 2012, Nucleic acids research.

[28]  Leonid A. Mirny,et al.  Compaction and segregation of sister chromatids via active loop extrusion , 2016 .

[29]  T. Hirano,et al.  HEAT repeats – versatile arrays of amphiphilic helices working in crowded environments? , 2016, Journal of Cell Science.

[30]  D. Jackson,et al.  The size of chromatin loops in HeLa cells. , 1990, The EMBO journal.

[31]  D. Marenduzzo,et al.  Nonspecific bridging-induced attraction drives clustering of DNA-binding proteins and genome organization , 2013, Proceedings of the National Academy of Sciences.

[32]  Tetsuya J. Kobayashi,et al.  Balancing acts of two HEAT subunits of condensin I support dynamic assembly of chromosome axes. , 2015, Developmental cell.

[33]  T. Hirano,et al.  Condensin-Based Chromosome Organization from Bacteria to Vertebrates , 2016, Cell.

[34]  K. Maeshima,et al.  New insight into the mitotic chromosome structure: irregular folding of nucleosome fibers without 30-nm chromatin structure. , 2010, Cold Spring Harbor symposia on quantitative biology.