Anticancer mechanism revealed by yeast experiment

Okinawa: DNA strands, like shoelaces and long necklaces, may become intertwined and unraveled. During cell division, special enzymes are constantly sorting long and complicated DNA so that DNA does not become entangled. However, in cancer cells, this safety device actively works too much, and the cancer spreads out. Researchers at Okinawa Institute of Science and Technology (OIST) have revealed some of the challenges of how this enzyme works in fission yeast and how we can weaken the function of this enzyme in human cancer Did.

In this study, published in Journal of Biological Chemistry on January 11, 2019, researchers focused on type II DNA topoisomerase (abbreviation Topo II), which is known as a cancer treatment target. Topo II resolves the twist and entanglement of DNA while well recognizing the DNA chain structure which changes in the course of cell division. For cancer cells, the activity of Topo II is enhanced, which accelerates tumor growth. Anti-cancer drugs targeting topo II inhibit the function of this enzyme and inhibit cancer cell replication and cancer spread.

However, Topo II inhibitors do not necessarily bring about sufficient anticancer effect. In order to effectively use inhibitors, it was necessary to elucidate the basic mechanisms of Topo II’s way of working.

“Many researchers are doing topo-II research, but we mainly use human cells and higher eukaryotic cells,” says a researcher belonging to the OISTG 0 cell unit led by Professor Mitsuhiro Yanagida Dr. Yoshihiko Nakazawa who is the lead author of the paper. According to the doctor, the majority of the cell division mechanism of fission yeast has been preserved in humans and experimental manipulations can be done quickly and easily, so we decided to study topo II in fission yeast.

“If we can analyze the activity of Topo II in yeast in a short period of time it will be possible to apply that finding to human cells.Our research shows that yeast is a suitable model for screening of topo II inhibitors and for clinical application It turned out to be an effective way to connect, “Dr. Nakazawa said.

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