Biologists Discovery May Force Revision of Biology Textbooks: Novel Chromatin Particle Halfway Between DNA and a Nucleosome

Biologists Discovery May Force Revision of Biology Textbooks: Novel Chromatin Particle Halfway Between DNA and a Nucleosome

  10:16:00 AM    Science Lover

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Basic biology textbooks may need a bit of revising now that biologists at UC San Diego have discovered a never-before-noticed component of our basic genetic material.

Biologists have discovered a novel chromatin 
particle halfway between DNA and a nucleosome. 
While it looks like a nucleosome, it is in fact a 
distinct particle of its own, researchers say. 
(Credit: James Kadonaga, UC San Diego)

According to the textbooks, chromatin, the natural state of DNA in the cell, is made up of nucleosomes. And nucleosomes are the basic repeating unit of chromatin.

When viewed by a high powered microscope, nucleosomes look like beads on a string. But in the Aug. 19 issue of the journal Molecular Cell, UC San Diego biologists report their discovery of a novel chromatin particle halfway between DNA and a nucleosome. While it looks like a nucleosome, they say, it is in fact a distinct particle of its own.

"This novel particle was found as a precursor to a nucleosome," said James Kadonaga, a professor of biology at UC San Diego who headed the research team and calls the particle a "pre-nucleosome." "These findings suggest that it is necessary to reconsider what chromatin is. The pre-nucleosome is likely to be an important player in how our genetic material is duplicated and used."



The biologists say that while the pre-nucleosome may look something like a nucleosome under the microscope, biochemical tests have shown that it is in reality halfway between DNA and a nucleosome.

These pre-nucleosomes, the researchers say, are converted into nucleosomes by a motor protein that uses the energy molecule ATP.

"The discovery of pre-nucleosomes suggests that much of chromatin, which has been generally presumed to consist only of nucleosomes, may be a mixture of nucleosomes and pre-nucleosomes," said Kadonaga. "So, this discovery may be the beginning of a revolution in our understanding of what chromatin is."

"The packaging of DNA with histone proteins to form chromatin helps stabilize chromosomes and plays an important role in regulating gene activities and DNA replication," said Anthony Carter, who oversees chromatin grants at the National Institute of General Medical Sciences of the National Institutes of Health, which funded the research. "The discovery of a novel intermediate DNA-histone complex offers intriguing insights into the nature of chromatin and may help us better understand how it impacts these key cellular processes."

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Cellular Stress Can Induce Yeast to Promote Prion Formation

Cellular Stress Can Induce Yeast to Promote Prion Formation

  6:53:00 PM    Science Lover

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It's a chicken and egg question. Where do the infectious protein particles called prions come from? Essentially clumps of misfolded proteins, prions cause neurodegenerative disorders, such as mad cow/Creutzfeld-Jakob disease, in humans and animals. Prions trigger the misfolding and aggregation of their properly folded protein counterparts, but they usually need some kind of "seed" to get started.

Biochemists at Emory University School of Medicine have identified a yeast protein called Lsb2 that can promote spontaneous prion formation. This unstable, short-lived protein is strongly induced by cellular stresses such as heat. Lsb2's properties also illustrate how cells have developed ways to control and regulate prion formation. Research in yeast has shown that sometimes, prions can actually help cells adapt to different conditions.

The results are published in the July 22 issue of the journal Molecular Cell. The senior author is Keith Wilkinson, PhD, professor of biochemistry at Emory University School of Medicine The first author is senior associate Tatiana Chernova, PhD.

The aggregated form of proteins connected with several other neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's can, in some circumstances, act like prions. So the Emory team's finding provides insight into how the ways that cells deal with stress might lead to poisonous protein aggregation in human diseases.

"A direct human homolog of Lsb2 doesn't exist, but there may be a protein that performs the same function," Wilkinson says. "The mechanism may say more about other types of protein aggregates than about classical prions in humans, This mechanism of seeding and growth may be more important for aggregate formation in diseases such as Huntington's."



Lsb2 does not appear to form stable prions by itself. Rather, it seems to bind to and encourage the aggregation of another protein, Sup35, which does form prions.

"Our model is that stress induces high levels of Lsb2, which allows the accumulation of misfolded prion proteins," Wilkinson says. "Lsb2 protects enough of these newborn prion particles from the quality control machinery for a few of them to get out."

The research was supported by the National Institutes of Health.

More information: T.A. Chernova et al. Prion Induction by the Short-lived Stress Induced Protein Lsb2 Is Regulated by Ubiquitination and Association with the Actin Cytoskeleton Mol. Cell (2011).
Provided by Emory University

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