When DNA Breakage Controls Brain Function: A New Role for TDP2 and TOP2β in Neuronal Gene Regulation
What if the ability of neurons to communicate, adapt, and maintain normal brain function depends partly on how efficiently they repair DNA breaks?
What if the ability of neurons to communicate, adapt, and maintain normal brain function depends partly on how efficiently they repair DNA breaks?
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 […]
A remarkable new study from investigators at the National Institutes of Health has uncovered an unexpected mechanism underlying one of chemotherapy’s most debilitating side effects: cisplatin-induced peripheral neuropathy. Rather than DNA repair simply protecting neurons, the researchers found that DNA repair itself can become toxic when neurons lack sufficient deoxynucleotide (dNTP) pools to complete the repair process. Their […]
OK, this paper actually has massive implications for topoisomerase drug discovery because it challenges a long-standing assumption about TOP2 poisons. Rather than simply trapping the cleavage complex (as etoposide does), the authors propose that their modified epipodophyllotoxin derivative actively dismantles the TOP2β catalytic apparatus, producing an irreversible, religation-defective complex that leads to persistent DNA double-strand breaks. Topoisomerase […]
A newly published study in Molecular Cell highlights an exciting advance in topoisomerase biology and potential cancer therapeutics. Importantly, this work was enabled using topoisomerase reagents and assay technologies supplied by TopoGEN. Konada and colleagues report that Heat Shock Factor 1 (HSF1) selectively stimulates the catalytic activity of DNA topoisomerase IIβ (TOP2β) while exerting minimal effects on […]
A new study published in Nature Structural & Molecular Biology provides important insights into how cells repair DNA damage arising from collapsed replication forks—one of the most significant threats to genome stability and a key driver of cancer, aging, and genetic disease. The authors demonstrate that repair outcomes differ dramatically depending on whether a single replication fork […]
A newly published study in Scientific Reports describes the identification and characterization of alternariol monomethyl ether (AME), a fungal secondary metabolite isolated from Alternaria alternata, with potent antiproliferative activity linked to inhibition of both DNA Topoisomerase I and II. Importantly, the investigators utilized TopoGEN’s plasmid relaxation and kDNA decatenation assay systems to quantify enzyme inhibition kinetics and demonstrate […]
There is an increasingly important enabling technology in gene therapy and nucleic acid delivery: the use of DNA Gyrase to generate highly supercoiled plasmid DNA, a topology that is strongly correlated with improved delivery efficiency and functional expression and enhanced efficiency in gene therapy.
Recent work published in Geroscience highlights an unexpected connection between topoisomerase inhibitors and longevity biology.
A new Phytomedicine (2026) study caught my attention—not because it shows anti-melanoma activity (we’ve seen that before), but because it begins to unpack how a plant-derived formulation enhances the efficacy of temozolomide (TMZ).