How changes in the DNA-cutting enzyme Topoisomerase II may cause cancer-linked mutations
Biochemical determinants of genome instability induced by eukaryotic topoisomerase II
This project looks at how specific changes in a DNA-cutting enzyme produce the small DNA duplications seen in some cancers.
Quick facts
| Grant type | R03 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Illinois at Chicago NIH-funded |
| Lab location | 1 site (Chicago, UNITED STATES) |
| Project ID | NIH-11261613 on NIH RePORTER |
What this research studies
Researchers will study mutant forms of the Topoisomerase II enzyme, including a human-linked mutation, using purified proteins and yeast models to see how the enzyme makes and leaves DNA breaks. They will measure enzyme-DNA cleavage intermediates and track the types of small duplications that appear when these mutants are present. The team will compare the mutation patterns they create to a known cancer mutational signature called ID17. The goal is to understand the biochemical steps that lead to genome instability tied to some tumors.
Who could benefit from this research
Good fit: Patients whose tumors show the ID17 mutational signature or who carry mutations in the TOP2A gene (for example K743N) would be most relevant for sample donation or future clinical follow-up.
Not a fit: People without cancers linked to topoisomerase-related mutation patterns or those seeking immediate treatment are unlikely to get direct benefit from this lab-focused project.
Why it matters
Potential benefit: If successful, this work could clarify how certain cancers acquire specific mutation patterns and point toward biomarkers or safer use of topoisomerase-targeting drugs.
How similar studies have performed: Prior lab work by this team and others has shown that mutant Top2 proteins cause similar small duplications in yeast and biochemical assays, but translating that to patient care has not yet been achieved.
Where this research is happening
Chicago, UNITED STATES
- University of Illinois at Chicago — Chicago, United States (Active)
Researchers
- Principal investigator: Nitiss, John L — University of Illinois at Chicago
- Study coordinator: Nitiss, John L
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.