New insight into cancer defense mechanism

The process, known as chromosome segregation, is vitally important because incorrect passage of the genomic material makes cells prone to develop into cancer cells. The discovery identified by Lundbeck Foundation Junior Group Leader Fellow Jakob Nilsson and his research team depends on a protein called BubR1 that is mutated in certain cancers.

Chromosome segregation

The research provides new insight into how our genetic material in form of chromosomes is safely segregated into each of the two new daughter cells that arises when a cell divides. This is a fundamental biological question that has been pursued for more than 100 years because chromosome movements during cell division was some of the earliest structures observed in primitive light microscopes. During cell division, the chromosomes is attached to a remarkable scaffolding structure of proteins, the mitotic spindle, that coordinates the complicated task of ensuring that each new cell in the body receives the correct number of gene copies from its maternal cell.

New function of a known protein

It is known that when cancer cells divide, the genetic material is often not passed on correctly which allows the resulting daughter cells to develop more aggressive growth patterns and become more resistant to chemotherapy. However the underlying defects is in many cases unknown.

There has been a lot of interest in understanding chromosome segregation and also how this is regulated by the protein BubR1. We used sophisticated live cell microscopy to follow chromosome movements in human cells that had mutations in the BubR1 protein, in order to see how this affected chromosome segregation. This allowed us to determine when the cells did not move their chromosomes correctly” says Jakob Nilsson.

“Our work provides a completely new function to how this protein works in human cells, which demonstrates the novel concept that a protein, in this case BubR1, can have more than one function depending on where it is located in the cell” adds Jakob Nilsson.

Potential benefits

The hope is that this research will help in defining better strategies for cancer therapy and provide a better understanding of why chromosomes are often not correctly distributed to the new daughter cells in cancer.

“We know that BubR1 is mutated in certain human cancers so our work could help explain how BubR1 causes cancer when mutated. In the future it could be beneficial to analyze cancer patients for mutations in BubR1. Today, cancer treatment is often based on trial and error but in the future we hope to predict patients’ responses to various drug treatments, based on knowing the mutations present in the individual cancer tissue. Simply put, patients with mutations in BubR1 could be responsive to specific types of drugs and ideally, by analyzing patients for the presence of mutated BubR1, we will know which drugs to use in advance” says Jakob Nilsson, Associate Professor from the Novo Nordisk Foundation Center for Protein Research.

Picture: Microscopic view of a human cell undergoing chromosome segregation. The mitotic spindle is seen as a red scaffolding structure to which each chromosome (blue) is attached. BubR1 is located within the green structures known as kinetochores. The two red poles will eventually migrate to each of the two daughter cells, to where a complete set of chromosomes will be moved by the mitotic spindle.

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