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Johns hopkins researchers find link between cell's energy use and genome health

hich is generally inactive had little apparent impact when they removed it. "The yeast seemed relatively unscathed," said Boeke.

But when they knocked out the other one - called Asc2p - the yeast cells died. That made it clear that this enzyme is critical for survival.

Further analysis with high-power microscopes revealed that this second enzyme, Asc2p, was residing - unexpectedly -- in the part of the cell housing its genetic material - its chromosomes - rather than in the part of the cell - the mitochondria -- that harvests energy from sugar.

But why would an enzyme involved in generating energy live in the "wrong" part of the cell? A closer look at the chromosomal and non-chromosomal parts of the cell showed that although the enzyme itself is found only in the former, the chemical made by it is found in both places.

The question remained as to why the enzyme Asc2p and its chemical product, known as acetyl-CoA, are found near chromosomes.

Chromosomes contain both DNA, which contains genes, and proteins around which the DNA is wrapped for storage and support.

In addition to being used for energy, the acetyl part of acetyl-CoA also is used in controlling how tightly DNA is wrapped in the chromosomes. More acetyl on chromosomes leads to looser wrapped DNA. And locations along chromosomes that contain looser wrapped DNA appear to be regions where genes are turned on.

When the research team removed the enzyme Asc2p that makes acetyl-CoA from yeast cells, they predicted, if they were right about why the enzyme and its chemical product are found near chromosomes, that the chromosomes would have less acetyl-CoA. Less acetyl-CoA, they reasoned, could cause DNA to be more tightly wrapped in chromosomes, and this might lead to genes being turned off. That is exactly what they found when they looked at the more than 5,000 genes in the yeast cells lacking this enzyme. More than 70 percent of them were indeed
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Source:Johns Hopkins Medical Institutions


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