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Each human cell has two meters of DNA packed and folded into small loops inside of a small nucleus of 10 micrometers of diameter. This extreme compression creates tension in the DNA that is dissipated by an enzyme, Topoisomerase 2 (TOP2). TOP2 constantly cuts and reseal the DNA, relaxing torsions and knots as the cell folds and organizes its genome. Sometimes, TOP2 fails resealing its own breaks and leads to DNA damage, genetic aberrations and cancer. In addition, many effective cancer chemotherapeutic drugs act inhibiting the resealing of TOP2 breaks, but frequently patients treated with these drugs develop secondary cancers years after the treatment. I found that TOP2 breaks where DNA folds to form loops, making these regions vulnerable to genetic aberrations that lead to secondary cancers. The ultimate goal of my research is to understand how DNA organization and folding inside the nucleus impacts the genetic aberrations that drive cancer.