Journal
JOURNAL OF CELL BIOLOGY
Volume 166, Issue 6, Pages 775-785Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200406049
Keywords
chromosome structure; condensins; topoisomerase II; mitosis; SNIC
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Funding
- NIGMS NIH HHS [R01 GM042516, GM42516, GM53926, R01 GM053926] Funding Source: Medline
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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.
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