Inside each human cell, about two meters of genomic DNA must be accurately copied and equally transmitted to two daughter cells during cell division. To achieve this, the copied DNA is condensed into thick, short structures called mitotic chromosomes. However, how chromatin is organized and condensed to form mitotic chromosomes has long remained a major question in genetics and cell biology.
In a new Review published in Trends in Genetics , Professor Kazuhiro Maeshima, SOKENDAI graduate student Masa A. Shimazoe, and technical staff member Sachiko Tamura from the Genome Dynamics Laboratory at the National Institute of Genetics summarize historical models and recent progress in understanding mitotic chromosome formation.
In the 1970s, Ulrich K. Laemmli and colleagues found that even after histones were biochemically removed from mitotic chromosomes, an axial structure resembling the shape of chromosomes remained. This structure was called the chromosome scaffold. Based on this finding, the chromosome scaffold model proposed that non-histone proteins help determine chromosome structure. Later studies identified condensins and topoisomerase IIα as major components of the chromosome scaffold, and these proteins are now known to play important roles in shaping mitotic chromosomes.
Mitotic chromosomes are not simply formed from hierarchical structures containing regular 30-nm chromatin fibers. Instead, they are now understood as irregular and dynamic structures shaped by multiple molecular and physical mechanisms.
“Mitotic chromosome formation has often been explained by chromosome-associated proteins such as condensins and topoisomerase IIα. These proteins are certainly essential, but they are not the whole story,” said Maeshima. “In this Review, we wanted to connect these protein-based mechanisms with the physical properties of chromatin itself.”
The Review discusses how DNA loop formation by condensins, DNA entanglement and disentanglement by topoisomerase IIα, and physical forces such as electrostatic interactions of histone tails, linker histone H1, free Mg 2+ , and macromolecular crowding/depletion attraction contribute to mitotic chromosome formation.
One key idea proposed in the Review is that mitotic chromosomes may not be formed from scratch during cell division. Instead, pre-existing condensed chromatin domains in interphase nuclei may function as “building blocks.” These blocks may be gathered, crosslinked, and reorganized by condensins and physical forces to form mitotic chromosomes.
“This view connects interphase chromatin and mitotic chromosomes as continuous structures,” said Shimazoe. “Rather than building mitotic chromosomes from scratch, cells may use pre-existing chromatin domains as building blocks and reorganize them during mitosis.”
The Review provides a new framework for understanding mitotic chromosome formation, starting from the chromosome scaffold model and integrating modern views of condensins, topoisomerase IIα, and the physical properties of chromatin.
About National Institute of Genetics (NIG)
National Institute of Genetics (NIG) was established to carry out broad and comprehensive research in genetics. NIG contributes to the development of academic research as one of the inter-university research institutes constituting the Research Organization of Information and Systems (ROIS).
About the Research Organization of Information and Systems (ROIS)
ROIS is a parent organization of four national institutes (National Institute of Polar Research, National Institute of Informatics, the Institute of Statistical Mathematics and National Institute of Genetics) and the Joint Support-Center for Data Science Research. It is ROIS's mission to promote integrated, cutting-edge research that goes beyond the barriers of these institutions, in addition to facilitating their research activities, as members of inter-university research institutes.
Trends in Genetics
Literature review
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Mitotic chromosomes: from the chromosome scaffold model to condensins and physical forces
14-Sep-2026