The research follows the behaviour of tumour cells in hereditary cancers of the breast and ovaries in the course of chemotherapy, which in these cells intentionally causes damage to DNA – so-called double-strand breaks. During treatment both strands of the DNA helix are interrupted and these breaks need to be repaired. Hereditary breast cancer cells often carry a genetic mutation which prevents the correct repairing of breaks, so that after chemotherapy these cells die and the tumours recede. Obviously if the tumour cells find a way to repair breaks without errors, the tumour becomes resistant to treatment. It is precisely the gene Rif1, or rather its mutation, that decides the type of repair to the DNA, and thus the success of the treatment. “Our experiments suggest that a genetic mutation of the gene Rif1 can effectively cancel genetic changes causing faulty repairs to damaged DNA. Breaks caused by treatment can in this case be repaired with fewer errors and cancer cells can thus survive,” states Zimmermann.
The unique discovery of the function of the gene Rif1 opens up new possibilities for clinical research into cancers of breast and ovaries, and also brings greater opportunities for optimum prognoses and targeted individual treatment. From the results so far it appears that doctors can make use of the studied mutation of gene Rif1 in hereditary breast and ovary cancers when choosing an effective therapy. This hypothesis now has to be tested on mouse models of these tumours, and then directly on oncology patients. “Our research has so far been rather basic – we mainly dealt with describing the mechanism regulating repair of double-strand breaks. We did not work directly with tumour cells, but with genetically modified mouse cell lines,” explains Zimmermann.
Michal Zimmermann is a postgraduate student in the field of Genomics and Proteomics at the Faculty of Science of Masaryk University while at the same time being a research scientist at CEITEC MU in the laboratory of Ctirad Hofr, PhD. Since 2010, as part of his postgraduate studies Michal Zimmermann has also been part of the international team led by Prof. Titia de Lange at Rockefeller University in New York. He got to this prestigious international workplace thanks to the long-term cooperation between the laboratories of Dr. Hofr and Prof. Fajkus of CEITEC MU with the Laboratory for Cell Biology and Genetics at Rockefeller University in New York.
