Cells compact their DNA when starved of oxygen, nutrients

For cells to function normally, large parts of their DNA structure have to be open and accessible so molecules that read genetic code can produce instructions for making proteins. Now, researchers have discovered that when cells are starved of oxygen or nutrients, they compact their DNA, making it difficult for these normal functions to continue.
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The researchers developed a new technology that allowed them to locate individual molecules in the DNA that is tightly packed inside the nucleus of cells.

This starved state is seen in many of today’s common diseases like heart attack, stroke and cancer, say scientists from the Institute of Molecular Biology (IMB) at Johannes Gutenberg University Mainz (JGU) in Germany.

Together with colleagues from other research centers, they write about the discovery in the journal Genome Biology and suggest it offers some important new clues about these diseases and how to treat them.

When a person suffers a heart attack or stroke, it can cause long-term damage because the restricted blood supply to the heart and brain starves the affected cells of oxygen and nutrients – a condition known as ischemia. Oxygen starvation – or hypoxia – can also result from other disease conditions, such as in cancer tumors.

In the new study, the researchers discovered that under these starvation conditions, the DNA in the nucleus of the affected cells changes dramatically – it compresses into tight clumps. The result is that gene-reading molecules cannot access the genetic code, and the cell eventually stops working.

When this happens to cells in the heart, it leads to a heart attack; when it happens in the brain, it leads to a stroke.

Senior author Dr. George Reid, group leader at IMB, says he and his colleagues are very excited by this finding and explains:

“When you have a stroke, when you have a heart attack, this is likely to be what’s happening to your DNA. Now we know that this is what’s going on, we can start to look at ways of preventing this compaction of DNA.”

Another important feature of the work is the use of a new DNA-probing technology that some of the IMB authors developed to look into the DNA of cells at a level of detail that has never been achieved before.

New technology shows single molecules in cells’ DNA

The genetic code held inside the nucleus of cells does not comprise free-floating linear strands of DNA – it is held in a tightly packed structure of DNA and proteins called chromatin. Chromatin structure is highly organized in order to fit the DNA compactly inside the nucleus, and to allow access for gene expression and DNA processing.

But conventional microscopy does not have sufficient optical resolution to study the nanostructures of chromatin, note the researchers.

The new technology is a development of super-resolution light microscopy. It uses blinking dyes that bind to DNA and allow the researchers to look inside and around the chromatin complexes and define the location of individual molecules in the DNA of mammal cells.

The new technology is described in a separate paper published in the journal Experimental Cell Research.

Meanwhile, Medical News Today recently learned that scientists are developing a model that predicts how different people react to a drug depending on their genetic and metabolic makeup. The model is based on the fact that different people have different variations of the same gene, and these variations affect how their bodies metabolize or process a drug.

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