Decision letter: Chromosome mis-segregation and cytokinesis failure in trisomic human cells

Abstract

The DNA in a human cell is divided between forty-six structures called chromosomes. Before a cell divides, it copies every chromosome so that each daughter cell will have the same DNA as the parent cell. These chromosomes align in the center of the cell and then the matching chromosomes are separated and pulled to opposite ends. However, in some cases the separation process does not work properly, which can produce cells that either have too many, or too few, chromosomes. Abnormal numbers of chromosomes within cells—called aneuploidy—is a leading cause of miscarriage and birth defects in humans. Aneuploidy is also a common feature of cancer cells. It is common for the chromosomes in cancer cells to be distributed unequally when the cell divides. This phenomenon is known as chromosomal instability, but the link between aneuploidy and chromosomal instability in cancer cells is not fully understood. Here, Nicholson et al. used live-cell imaging techniques to analyze healthy human cells and cancer cells that had either the normal forty-six chromosomes, or a defined extra chromosome. Nicholson et al. found that when the cells divided, the chromosomes in the cells that had an extra copy of chromosome 7 or 13 were more prone to distributing chromosomes unequally, compared to cells with a normal number of chromosomes. Nicholson et al. also observed that the cells with an extra chromosome 13 were unable to properly divide into two. These cells had increased levels of a protein called Spartin—which is important for the last stage in cell division—and this was responsible for the failure to produce two daughter cells. These findings show that aneuploidy can cause chromosomal instability in human cells. Furthermore, Nicholson et al. have identified a defect in cell division that is specifically caused by the presence of an extra chromosome 13 in human cells. A future challenge will be to determine how, and to what extent, different chromosomes can affect chromosome stability. This could be useful in the development of therapies against cancer cells with aneuploidy.