University of Illinois Cancer Center Member John Nitiss, PhD, is among the UIC College of Pharmacy Rockford authors of the study, Naturally mutagenic sequence diversity in a human type II topoisomerase, published by the journal Proceedings of the National Academy of Sciences of the United States (PNAS).
PNAS Study Details
The researchers used genetic, biochemical and computational tools to characterize mutant forms of human topoisomerase IIβ (hTOP2β) that are hypersensitive to the chemotherapy drug etoposide. The mutant enzymes had the ability to induce spontaneous DNA damage that can lead to mutations and other genomic alterations. The mutations were applied to structural models that led to the identification of similar mutations in hTOP2β found in human cancers.
Topoisomerases are enzymes that break and reseal DNA to relieve the twisting stress that comes from cellular processes such as transcription and DNA replication. Because topoisomerases must break DNA during their reaction cycle, they have the potential to induce genome changes that may be deleterious, and may drive cancer progression.
“Our findings demonstrate that some hTOP2β mutations identified in cancer cell samples can exert deleterious activities in cellular contexts, underscoring the ability of topoisomerase dysfunction to disrupt genetic integrity,” researchers concluded.
Nitiss, part of the Cancer Center’s Cancer Biology research program, is the Assistant Dean for Research at the College of Pharmacy Rockford. The other UIC-affiliated authors are Karin Nitiss, PhD; Raveena Gupta, MS; and Ria Guha, MS. Other authors are from the Johns Hopkins University School of Medicine in Baltimore, Maryland.