Nucleation capacity and presence of centrioles define a distinct category of centrosome abnormalities that induces multipolar mitoses in cancer cells.

Analysis of centrosome number and structure has become one means of assessing the potential for aberrant chromosome segregation and aneuploidy in tumor cells. Centrosome amplification directly causes multipolar catastrophic mitoses in mouse embryonic fibroblasts (MEFs) deficient for the tumor suppressor genes Brca1 or Trp53. We observed supernumerary centrosomes in cell lines established from aneuploid, but not from diploid, colorectal carcinomas; however, multipolar mitoses were never observed.

Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase.

Polo-like kinases (PLKs) play critical roles throughout mitosis. Here, we report that wortmannin, which was previously thought to be a highly selective inhibitor of phosphoinositide (PI) 3-kinases, is a potent inhibitor of mammalian PLK1. Observation of the wortmannin-PLK1 interaction was enabled by a tetramethylrhodamine-wortmannin conjugate (AX7503) that permits rapid detection of PLK1 activity and expression in complex proteomes.

Polo-like kinase 1 inactivation following mitotic DNA damaging treatments is independent of ataxia telangiectasia mutated kinase.

Polo-like kinase 1 (Plk1) is an important regulator of several events during mitosis. Recent reports show that Plk1 is involved in both G2 and mitotic DNA damage checkpoints. Ataxia telangiectasia mutated kinase (ATM) is an important enzyme involved in G2 phase cell cycle arrest following interphase DNA damage, and inhibition of Plk1 by DNA damage during G2 occurs in an ATM-/ATM-Rad3-related kinase (ATR)-dependent fashion.