Longevity & AgingKey Enzyme TOP3A Found to Control Cancer's Telomere Survival Trick
Researchers at the NIH's National Cancer Institute identified topoisomerase IIIα (TOP3A) as a critical regulator of alternative lengthening of telomeres (ALT), a homologous-recombination-based mechanism that roughly 10–15% of cancers — including many osteosarcomas and glioblastomas — use to maintain telomere length and survive indefinitely. TOP3A was found exclusively enriched at telomeres in ALT cells (not telomerase-positive cells), where it stabilizes the protective shelterin complex, promotes TERRA RNA recruitment, and generates the single-stranded C-strand DNA signatures that define ALT. Knocking out TOP3A or deploying a toxic 'self-poisoning' mutant disrupted these telomeric structures, slowed cancer cell growth, and caused chromosome instability — pointing to TOP3A as a promising ALT-specific cancer drug target.
