A new study from Northwestern University and Sonoma State University (Sun et al., 2026, bioRxiv) provides direct physical evidence that mitotic chromosomes aren’t the fully separate units they appear to be under the microscope. Using micropipette manipulation to gently extract chromosomes from living HeLa and mouse fibroblast cells, the researchers found that pulling on a single chromosome sequentially drags out its neighbors — revealing thin, elastic “interchromosome linkers” tethered at the centromeres. These linkers proved to be DNA-based (destroyed by DNase, but untouched by RNase, protease, or spindle-poison colchicine), highly elastic, and mechanically robust enough to transmit tension across the genome.
TopoGEN reagents were central to pinning down the molecular identity of these structures. The team’s Topo IIα antibody (TG2011-1) was sprayed directly onto isolated, stretched linkers for immunofluorescence imaging, revealing that topoisomerase IIα is enriched on the linkers and organized into discrete, evenly spaced puncta roughly every 0.4 megabases — a pattern distinct from the diffuse condensin staining seen elsewhere on the chromosome. This positioned Topo IIα as a leading candidate for structurally organizing the linker DNA. Separately, TopoGEN’s kDNA decatenation assay was used to confirm the enzymatic activity of purified human Topo IIα before it was applied directly to linkers, testing (and ruling out) simple decatenation as the mechanism holding chromosomes together.
By combining micromechanical force measurements with these targeted reagents, the study builds a compelling case that chromosomes stay physically networked through mitosis via a Topo IIα-organized chromatin architecture — insight made possible only by tools sensitive enough to probe structures just tens of nanometers wide.
Mingxuan Sun, View ORCID ProfileRon Biggs, Omar Akhtar, View ORCID ProfileGabriel Quintero Plancarte, View ORCID ProfileLisa L. Hua, View ORCID ProfileJohn F. Marko
doi: https://doi.org/10.64898/2026.08.31.748267