Monday, January 30, 2012

MIT: Defective enzymes may spell higher cancer risk

By Lori Valigra

Errors in cellular systems that control purines, a key class of molecules in cells, can ripple down and severely alter a cell’s DNA sequences, causing some people carrying the resulting purine genetic variants to have a higher risk for certain cancers, MIT biological engineers reported today.

The researchers disrupted about half a dozen purine metabolism enzymes in E. coli and yeast and found that malfunctioning enzymes could produce high levels of a nucleotide called hypoxanthine. When hypoxanthine and another nucleotide called xanthine are mistakenly inserted into DNA, they cause mutations. They also can interfere with the function of messenger RNA, which carries DNA’s instructions to the rest of the cell, as well as the RNA molecules that translate mRNA into proteins.

The results were published in the Jan. 30 edition of the Proceedings of the National Academy of Sciences.

Many critical cell functions depend on purines. They are a major component of the chemicals that store a cell’s energy. Cells keep tight control over their purine supply, and any disruption can have serious consequences, according to information supplied by MIT.

“A cell needs to control the concentrations very carefully so that it has just the right amount of building blocks when it’s synthesizing DNA. If the cell has an imbalance in the concentrations of those nucleotides, it’s going to make a mistake,” Peter Dedon, professor of biological engineering at MIT and senior author of the study, said in a statement.

Scientists have found quite a bit of genetic variation in purine metabolic enzymes in humans, so the research team plans to look into the impact of those variants on xanthine and hypoxanthine insertion into DNA.