A new paper derived from international collaboration between Hiroshima University-HiHA (Masaru Ueno group) and University of Sussex, UK (Jo Murray group) was published in PLoS ONE.
Authors: Shamim HM, Minami Y, Tanaka D, Ukimori S, Murray JM, Ueno M.
Title: Fission yeast strains with circular chromosomes require the 9-1-1 checkpoint complex for the viability in response to the anti-cancer drug 5-fluorodeoxyuridine.
PLoS One. 2017 Nov 9;12(11):e0187775. doi: 10.1371/journal.pone.0187775. eCollection 2017.
Background: It is known that many cancer cells carry circular chromosomes, instead of linear ones. However, it remains elusive as to how these circular chromosomes are maintained through cell divisions.
Results: In this work, using fission yeast that carry circular chromosomes as a model, the authors have investigated the mechanism by which circular chromosomes are maintained and also explored the physiology of cells carrying circular chromosomes. They have found that the 9-1-1 complex (Rad9-Rad1-Hus1), an important factor for DNA damage checkpoint signaling, becomes essential for the survival of cells carrying circular chromosomes in the presence of 5-fluorodeoxyuridine (Fudr). Fudr is an anti-cancer drug used clinically in the USA for treatment of kidney cancer. Furthermore, the authors have found that Fudr on its own blocks DNA replication in fission yeast cells despite that this yeast does not have a target (thymidine kinase) for Fudr.
Implications：These results point towards an interesting possibility that cancer cells carrying circular chromosomes (eg. atypical lipomatous tumors and dermatofibrosarcoma protuberant tumors) could be selectively killed by the combined usage of inhibitors for DNA damage checkpoint and DNA replication.