Plk4 Is Required for Cytokinesis and Maintenance of Chromosomal Stability
Plk4 is required for cytokinesis and maintenance of chromosomal stability Carla O. Rosarioa,b, Michael A. Koa,c,d,1, Yosr Z. Haffania,1, Rebecca A. Gladdya,c,d, Jana Paderovae, Aaron Pollettb, Jeremy A. Squiree, James W. Dennisa,b,f, and Carol J. Swallowa,b,c,d,2 aSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; bDepartment of Laboratory Medicine and Pathobiology, cDepartment of Surgery, dInstitute of Medical Science, and fDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada; and eDepartment of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada Edited by David Pellman, Dana-Farber Cancer Institute, Boston, MA, and accepted by the Editorial Board February 16, 2010 (received for review September 25, 2009) Aneuploidy is a characteristic feature of established cancers and dumbbell-shaped cells with anaphase bridges, indicating that can promote tumor development. Aneuploidy may arise directly, Plk4 is also required in late mitosis, possibly at telophase (8). − through unequal distribution of chromosomes into daughter cells, Plk4+/ embryos develop normally, but adult mice display a 16- or indirectly, through a tetraploid intermediate. The polo family fold increase in the incidence of spontaneous hepatomas com- kinase Plk4/Sak is required for late mitotic progression and is pared with Plk4+/+ littermates. The wild-type Plk4 allele was haploinsufficient for tumor suppression in mice. Here we show retained in the liver tumors, indicating that Plk4 is a hap- that loss of heterozygosity (LOH) occurs at the Plk4 locus in 50% of loinsufficient tumor suppressor (9). Cell cycle progression was − human hepatocellular carcinomas (HCC) and is present even in impaired in regenerating Plk4+/ liver with a ≈6-h delay in M preneoplastic cirrhotic liver nodules.
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