New Insight into the Mitotic Chromosome Structure: Irregular Folding of Nucleosome Fibers Without 30-nm Chromatin Structure

Abstract

Mitotic chromosomes are essential structures for the faithful transmission of replicated genomic DNA into two daughter cells during cell division. A long strand of DNA is wrapped around a core histone and forms a nucleosome. The nucleosome has long been assumed to be folded into 30-nm chromatin fibers. However, how the nucleosome or 30-nm chromatin fiber is organized into mitotic chromosomes remains unclear, although condensins and topoisomerase IIα are implicated in the condensation process. In fact, what do mitotic chromosomes look like in living cells? When frozen hydrated human mitotic cells were observed using cryo-electron microscopy (cryo-EM), higher-order structures including 30-nm chromatin fibers were not found. We thus propose that the nucleosome fibers in the bulk of mitotic chromosomes do not form 30-nm chromatin fibers but instead exist in a highly irregular state that is locally similar to a polymer melt. We provide new insight into mitotic chromosome structure.