Award
National Cancer Institute 5F31CA294935-02
Topologically complex DNA substrates to aid structure determination of the human topoisomerase IIa
Recipient
Johns Hopkins University, Baltimore, MD, United States
Award Amount
$50,114.00
Ceiling
$50,114.00
Awarded
July 08, 2026
Identifier
5F31CA294935-02
This award funds research to study the structure and mechanism of human topoisomerase IIa using complex DNA substrates, aiming to improve understanding of its role in genome stability and cancer drug interactions.
Description
Dysregulation of the DNA topoisomerase II (TOP2) catalytic cycle can lead to genome instability and cytotoxicity that are both exploited by and byproducts of certain anti-cancer drugs. A deeper understanding of how TOP2s physically pass DNA segments through one another depends on structural and biophysical studies in the presence of native-like, topologically complex DNA substrates such as chromatinized or supercoiled DNA. The proposed research will not only advance our understanding of TOP2 mechanism and biology, but also better establish how different classes of drugs bind to TOP2A in an unbiased manner, thereby advancing efforts to better target TOP2 for therapeutic intervention.