The January 2018 Editor's Choice Article is “Thiopurine-induced mitotic catastrophe in Rad51d-deficient mammalian cells” by Michael D. Wyatt, Nicole M. Reilly, Shikha Patel, Preeti Rajesh, Gary P. Schools, Phillip G. Smiraldo, and Douglas L. Pittman.
Dr. Wyatt and colleagues reported studies that examined the connections between the chemotherapeutic and immunosuppressive drug, 6-thiopurine, the telomeric caps on the ends of chromosomes and a DNA repair protein RAD51D. 6-thiopurine was shown to destabilize telomeres, inducing a protective RAD51D-dependent DNA damage response. Cells that were deficient for expression of RAD51D were more sensitive to 6-thioguanine than normal cells and demonstrated increased signals of the DNA damage response biomarker, gamma-H2AX, at telomeres. 6-thioguanine induces chromosomal fusions that may break at mitosis. Thiopurine-treated cells that entered mitosis display prolonged progression and many failed to complete segregation of chromosomes and cell division. This mitotic catastrophe led to the development of multinucleated surviving cells, an abnormal condition often seen in cancer. This work emphasizes the complexity of mechanisms of cell killing by cancer chemotherapeutic drugs, the many DNA repair pathways that influence cellular outcomes, and untoward side-effects of therapy. Environ. Mol. Mutagen. 59:38–48, 2018. © 2017 Wiley Periodicals, Inc.