New leap for cancer research

A U research team believes its discovery on a medical mystery could lead to new cancer drugs.

Keaton Schmitt

Mutant yeast might be the key to a long-standing puzzle in cancer research and could potentially lead to new anti-cancer drugs.
 
 
A team of researchers at the University of Minnesota released a study last week on the yeast’s ability to reproduce even when its DNA is incorrectly replicated, an ability shared by cancer cells. 
 
 
Unlike normal cells, cancer cells reproduce even if their DNA is copied incorrectly, said Naoko Shima, a University genetics professor. Normally, cells are forced to go through “checkpoints” that stop cell reproduction if it has DNA errors. 
 
 
“Checkpoints can sense something went wrong before cells divide. … [Cells] activate that checkpoint, but then these mutant cells somehow override the checkpoint,” Shima said.
 
 
Scientists have been unsure for years why cancer can survive faulty replication when checkpoints should stop it, said study co-author Yee-Mon Thu.
 
 
“In normal cells, there are some pathways to buffer [DNA errors], but oftentimes they die. … In cancer cells, they tolerate this process,” Thu said. 
 
 
The group thinks it might have solved that mystery and published their findings in Cell Reports last week.
 
 
The researchers made mutant yeast copy its DNA incorrectly then compared it to normal yeast, Thu said. Like cancer, the mutant yeast survived DNA errors and bypassed checkpoints.
 
 
“[Replication errors], we can trigger that. It’s basically like turning a dial up and down. By growing it at a higher or lower temperature you can very well dose the amount of faulty replication,” said Anja-Katrin Bielinsky, a co-author on the study and Masonic Cancer Center program co-director.
 
 
The team found higher-than-normal levels of a protein in the mutant cells, Thu said. This protein turns off one of the checkpoints, allowing mutant cells through even if they have errors.
 
 
She said other researchers could design drugs to decrease the amount of this protein, which means faulty mutant cells could be stopped at the checkpoints.
 
 
Bielinsky said this protein is also present in human and cancer cells, meaning the drugs could slow cancer growth.
 
 
While the protein is present in normal and mutant cells, in the mutant cells the protein has an additional piece added, she said. This addition starts the process that shuts down the checkpoint.
 
 
The team used a process called mass spectrometry to find the added piece, said LeeAnn Higgins, University researcher and co-author on the study.
 
 
“You basically have a sample of unknown biochemical and the mass spectrometer lets you find out what they are,” Higgins said.
 
 
She said researchers can use mass spectrometry to identify molecules by giving them a charge so a machine can measure its mass.
 
 
When they measured the molecules, the team found differences on the yeast mutants, which told them there was an additional piece.
 
 
Bielinsky said the team has worked over the past year on preliminary research on mice cells, and once they publish those findings they want to turn their attention to human treatments.