This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Inside each human cell, about 2 meters (6.6 feet) 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, Kazuhiro Maeshima, a professor; 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.
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 nonhistone 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," Maeshima said. "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 Mg2+, 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," Shimazoe said.
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