JUN 06, 2018 5:48 PM PDT

New Role for Protein Complex Provides Insight Into Cancer Development

WRITTEN BY: Carmen Leitch

When our cells have to divide, all the genetic material they contain must be duplicated and then properly distributed to the two new cells so that each one gets 23 pairs of chromosomes. When that process goes awry in a developing organism, it can lead to serious developmental disorders; it is also associated with cancer. Now, researchers have revealed more about the molecular processes underlying chromosome segregation, which provides insight into why aggressive kidney tumors develop in some children. The work has been reported in The Journal of Cell Biology.

"When a cell makes a decision to divide it needs to make sure its DNA is equally segregated between both daughter cells," explained Tina Sing, who led this work in the lab of Professor Grant Brown at the Donnelly Centre and Department of Biochemistry at the University of Toronto. "The cells must first replicate their DNA and then they have to pull apart these two copies of the DNA so that each daughter cell receives one complete copy of the entire genome."

There are a number of diseases caused by the uneven distribution of chromosomes. People with an extra copy of chromosome 21 have Down syndrome. Women who lack the second copy of the X chromosome are sterile; a disorder called Turner syndrome. Chromosomal abnormalities are also often seen in cancer cells that can outgrow normal cells.

Related: A Pair of Genomes is Best

Sing, now a postdoctoral researcher at Berkeley, found that protein machinery used by the cell called the ‘risk complex’ for RSC (remodels the structure of chromatin), helps to split up the chromosomes evenly when a cell divides into daughter cells. RSC does this by helping to form a cellular structure called a centrosome, which acts to pull chromosomes apart. 

"We found that if cells lack RSC function then this causes abnormal DNA segregation and a spontaneous doubling of chromosome number in cells," said Sing.

In this research, Sing and Brown used a budding yeast model to show that when RSC is not working, the yeast cells behave as cancer would. The cells also had an unusually high number of chromosomes and had too many centrosomes. The yeast with mutated RSC had far more than the usual two centrosomes per cell, making the even separation of chromosomes extremely challenging.

RSC has been known as a molecule that helps control the expression of genes. This work ties other groups' findings on the protein complex in with a role for segregating chromosomes. It may indicate how one kind of childhood cancer forms.
 
When humans have certain mutations in their RSC gene, chromosome number can go up spontaneously. Such mutations have also been identified in very aggressive kidney cancer tumor cells. Yeast has helped show how these events might happen.

"It's always surprising to think about how fundamental processes in yeast also take place in humans," Sing noted. "We think that our study gives some insight into this observation in cancer cells and we think it's possible that this complex is also helping with chromosome segregation in human cells."

Sing started by looking at the known roles of RSC, but during that study, found that in cells where RSC wasn’t active, there were too many chromosomes. "The increase in chromosomes was more interesting than what we were looking for," she said. "I think the study is a good example of how sometimes when you set out to study a specific biological problem you can be surprised by the data that you find and sometimes just following your curiosity down a different path can lead to understanding another aspect of biology."


Sources: AAAS/Eurekalert! Via University of Toronto, Journal of Cell Biology 

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
MAR 12, 2020
Cell & Molecular Biology
MAR 12, 2020
Zika Virus Used to Treat Advanced Tumors in Dogs
Researchers found a use for the zika virus; they treated advanced tumors of the central nervous system of three elderly ...
MAR 28, 2020
Cancer
MAR 28, 2020
The Not So Minor Genetic Players in Head and Neck Cancers
Head and neck squamous cell carcinomas (HNSCC) are among the most prevalent cancers among smokers, linked to alcohol con ...
APR 21, 2020
Cell & Molecular Biology
APR 21, 2020
Virtual Cell Provides a Close Look at Gene Expression During Development
Living organisms start out as one cell, and its genetic programs allow it to divide many times over, to give rise to the ...
MAY 11, 2020
Cell & Molecular Biology
MAY 11, 2020
3D Cell Culture Model Suggests Herpes Can Cause Alzheimer's
Alzheimer's is a common form of dementia that affects as many as 5.5 million Americans and the incidence is increasing a ...
MAY 17, 2020
Cell & Molecular Biology
MAY 17, 2020
Potential Treatment for Brain and Spinal Cord Injury is IDed
Treatment options are limited for people that have suffered swelling-inducing injuries to their brain and spinal cord. N ...
MAY 20, 2020
Clinical & Molecular DX
MAY 20, 2020
QMS Competencies Your Reagent Supplier Should Possess
The ability of a clinical laboratory to provide consistent and reliable results to their customers depends on the consis ...
Loading Comments...