How DNA Is Damaged by Enzyme Errors

New investigation reveals critically-important cellular mechanisms

Some people are at higher risk of developing cancer as a result of DNA damage than others, and a team of investigators at the Massachusetts Institute of Technology (MIT) believes it may have just discovered the mechanism behind this connection.

In the study, the group focused its attention on a class of molecules called purines. These biochemical compounds play an important role in underlying the structure of DNA and RNA, making up as much as half of their building blocks.

In addition, they are also important components in the chemicals that allow cells to store and use their energy supplies. But the purine production process is itself controlled by various enzymes, specialized proteins that can easily act as catalyst for various reactions.

What the MIT group found was that disruptions in the purine supply chain could lead to a host of negative, extremely-serious side effects, such as for instance the development of cancer and extensive damage to genetic material.

Biological engineers at the institute say that the enzyme systems controlling purine production and absorption can sometimes break down due to the fact that they are controlled by unusual variants of the standard enzymes. These mutated molecules are only found in a minority of the population.

These are the exact same people that are at a higher risk of developing certain types of cancer. “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,” scientist Peter Dedon explains.

“If the cell has an imbalance in the concentrations of those nucleotides, it’s going to make a mistake,” adds the investigator, who is the senior author of the research. The work is published in the January 30 issue of the esteemed journal Proceedings of the National Academy of Sciences (PNAS).

Dedon holds an appointment as a professor of biological engineering at MIT. He explains that one of the most important functions of purines is making up portions of ATP (adenosine triphosphate), the main energy currency of the human body.

Investigators with other research groups say that this study opens the way to a new understanding of how abnormalities in critical enzyme systems are involved in producing diseases.

“This paper opens the door to numerous studies – for example, looking into the biological effects resulting from the accumulation of abnormal bases in DNA and RNA,” Oregon State University professor emeritus of biochemistry and biophysics Chris Mathews says. He was not a part of the study.

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