CELL BIOLOGY: Aneuploidy in the Balance

Prasad V. Jallepalli¹ and David Pellman
A central principle of genetics is that cells within an organism contain the same complement of chromosomes. The presence of too many or too few chromosomes, called aneuploidy, is associated with disease, and accounts for the majority of spontaneous miscarriages in humans, as well as hereditary birth defects such as Down syndrome (1). Precisely how aneuploidy affects cells is not well understood. Extra chromosomes cause a proportionate increase in gene expression (2), potentially altering a cell's dosage of proteins in damaging ways. On the other hand, most cancer cells are aneuploid, suggesting that some patterns of chromosome gain and loss enable cells to escape normal growth restraints and develop into malignant tumors--for example, by acquiring extra copies of an oncogene, or losing a tumor suppressor gene (3, 4). But are the effects of aneuploidy strictly specific to a given over- or underrepresented chromosome, or does aneuploidy evoke a generalized physiological response regardless of what chromosome is affected? A new study by Torres et al. (5) on page 916 of this issue uncovers characteristics shared by all aneuploid cells, identifying a broad cellular response to aneuploidy that has ramifications for better understanding aneuploidy-linked diseases in humans.