Centromere structure and chromosome segregation errors

Researchers made a surprising new discovery in the structure of the centromere, a structure that is involved in ensuring that chromosomes are segregated properly when a cell divides. Mistakes in chromosome segregation can lead to cell death and cancer development.

The researchers discovered that the centromere consists of two subdomains. This fundamental finding has important implications for the process of chromosome segregation and provides new mechanisms underlying erroneous divisions in cancer cells. The research was published in Cell.

Our bodies consist of trillions of cells, most of which have a limited life span and therefore need to reproduce to replace the old ones. This reproduction process is referred to as cell division or mitosis. During mitosis, the parent cell will duplicate its chromosomes in order to pass down the genetic material to the daughter cells. The resulting identical pairs of chromosomes, the sister chromatids, are held together by a structure called the centromere. The sister chromatids then need to be evenly split over the two daughter cells to ensure that each daughter cell is an exact copy of the parent cell. If errors happen during the segregation, one daughter cell will have too many chromosomes, while the other has too few. This can lead to cell death or cancer development.

The centromere is a part of the chromosome that plays a vital role in chromosome segregation during mitosis. The process of dividing the sister chromatids over the cells is guided by the interaction between the centromeres and structures known as spindle microtubules. These spindle microtubules are responsible for pulling the chromatids apart and thus separating the two sister chromatids.

The first author of this study, explains: ‘If the attachment of the centromere to the spindle microtubules does not occur properly it leads to chromosome segregation mistakes which are frequently observed in cancer.’ Understanding the structure of the centromere can contribute to more insights into the function of the centromere and its role in erroneous chromosomal segregation.

To investigate the centromere structure, the researchers used a combination of imaging and sequencing techniques. Previously believed to consist of a compact structure attaching to multiple spindle microtubules, it was instead revealed that the centromere consists of two subdomains.

The author explains: ‘This discovery was very surprising, as subdomains bind microtubules independently of each other. Yet, to form correct attachments, they must remain closely connected. In cancer cells, however, we often observe that subdomains uncouple, resulting in erroneous attachments and chromosome segregation errors.'