p53 censuses centrosomes

p53 guards the genome by preventing cells with abnormal numbers of centrosomes from dividing, Lambrus et al. show.

In each cell cycle, a cell duplicates its centrosome, producing a pair of the structures that can serve as the poles of the mitotic spindle. Cancer or developmental defects can stem from mistakes in duplication that result in cells carrying an incorrect number of centrosomes. However, researchers haven’t been able to confirm that centrosomes help organize the mitotic spindle.

To address this question, Lambrus et al. used a technique that allowed them to remove centrosomes at precise times. They outfitted Polo-like kinase 4 (Plk4), a protein that controls centrosome duplication, with a segment known as a degron. Adding a plant hormone spurs the destruction of proteins carrying this segment, and the researchers found that the technique rapidly cut Plk4 levels and blocked centrosome duplication. When the researchers prolonged the depletion of Plk4, cells would divide a couple of times before the cell cycle halted permanently. However, the usual suspects to trigger this growth arrest—DNA damage, improper separation of chromosomes, and prolonged mitosis—weren’t responsible. Lambrus et al. hypothesized that cells have a centrosome surveillance system to protect against harmful mitoses that arise from divisions with the wrong number of centrosomes.

The researchers found that if they depleted the tumor suppressor p53, cells that chronically lacked Plk4 could divide without centrosomes. These cells made more errors during mitosis, emphasizing the importance of the surveillance mechanism. The next step for researchers is to discover how a cell senses when it’s short on centrosomes.