title: Visualization of early chromosome condensation: a hierarchical folding, axial glue model of chromosome structure.
abstract: Current models of mitotic chromosome structure are based largely on the examination of maximally condensed metaphase chromosomes. Here, we test these models by correlating the distribution of two scaffold components with the appearance of prophase chromosome folding intermediates. We confirm an axial distribution of topoisomerase IIalpha and the condensin subunit, structural maintenance of chromosomes 2 (SMC2), in unextracted metaphase chromosomes, with SMC2 localizing to a 150-200-nm-diameter central core. In contrast to predictions of radial loop/scaffold models, this axial distribution does not appear until late prophase, after formation of uniformly condensed middle prophase chromosomes. Instead, SMC2 associates throughout early and middle prophase chromatids, frequently forming foci over the chromosome exterior. Early prophase condensation occurs through folding of large-scale chromatin fibers into condensed masses. These resolve into linear, 200-300-nm-diameter middle prophase chromatids that double in diameter by late prophase. We propose a unified model of chromosome structure in which hierarchical levels of chromatin folding are stabilized late in mitosis by an axial "glue."
authors.affiliation: Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Natashe
authors.initials: N
authors.lastname: Kireeva
authors.forename: Margot
authors.initials: M
authors.lastname: Lakonishok
authors.forename: Igor
authors.initials: I
authors.lastname: Kireev
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hirano
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Belmont
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm; D016466:CHO Cells; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D002842:Chromatids / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D002843:Chromatin / Q000378:metabolism / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism* / Q000648:ultrastructure; D002875:Chromosomes / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D006224:Cricetinae; D003412:Cricetulus; D003432:Cross-Linking Reagents; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008961:Models, Structural; D046912:Multiprotein Complexes; D011418:Prophase
chemical_list: D000951:Antigens, Neoplasm; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C108312:condensin complexes; D000251:Adenosine Triphosphatases; D004250:DNA Topoisomerases, Type II